Financial burden and physical and emotional quality of life in COPD, heart failure, and kidney failure.

Patients with chronic and serious illnesses experience significant quality of life concerns. More research is needed to understand the impact of financial burden on patients with COPD, heart failure, and kidney failure. Patients with COPD, heart failure, or kidney failure completed a cross-sectional online survey using validated measures of financial burden (general financial strain as well as financial toxicity attributable to treatment), physical quality of life (symptom burden and perceived health), and emotional quality of life (anxiety, depression, and suicidal ideation). ANCOVA was used to examine whether financial strain and financial toxicity were associated with physical and emotional quality of life, while accounting for key covariates. Among 225 participants with COPD (n = 137), heart failure (n = 48), or kidney failure (n = 40), 62.2% reported general financial strain, with 34.7% experiencing financial toxicity attributable to treatments. Additionally, 68.9% rated their health as fair or poor, experiencing significant symptom burden including fatigue, dyspnea, and chest pain. Participants also reported clinically relevant levels of anxiety (55.1%), depression (52.0%), and suicidal ideation (21.8%). In the total sample, financial strain was associated with worse physical and emotional quality of life on all measures (all Ps < .001). Financial toxicity attributable to treatment was not associated with quality of life in the total sample or subsamples. Patients with COPD, heart failure, and kidney failure face significant financial, physical, and emotional burdens. Financial strain appears to undermine physical and emotional quality of life. Our study highlights the demand for interventions aimed at mitigating financial strain and toxicity experienced by individuals with chronic illnesses.

Concurrent Acute Heart Failure and Renal Failure in Amyloid Light Chain Amyloidosis.

INTRODUCTION: Amyloid light chain (AL) amyloidosis is a multisystem disease with significant variability in patient presentation. This case describes the presentation and workup of a patient with unique multiorgan involvement on initial presentation. CASE PRESENTATION: A 69-year-old African American male presented with weakness, leg swelling, and shortness of breath. Initial workup demonstrated acute heart failure and acute-on-chronic renal failure with nephrotic range proteinuria (5.78 protein to creatinine ratio). Further workup showed elevated serum protein electrophoresis, urine protein electrophoresis, and light chains. Subsequent renal biopsy showed lambda-restricted AL-type renal amyloidosis. DISCUSSION: A variety of systemic presentations have been described in the literature; however, concurrent heart and renal failure as primary presentation is uncommon. CONCLUSIONS: This case emphasizes the importance of considering systemic inflammatory diseases, such as amyloidosis, in the differential diagnoses of patients with unexplained multiorgan disease. Early diagnosis and treatment initiation are essential for improving patient outcomes. Improved recognition of common clinical manifestations and laboratory abnormalities will likely improve outcomes through earlier diagnosis.

Prognosis of concurrent renal impairment at diagnosis of multiple myeloma: a systematic review.

BACKGROUND: Multiple myeloma is a malignant tumour of the blood in which abnormal proliferation of plasma cells leads to bone destruction, renal impairment, anaemia, and hypercalcaemia. Renal impairment caused by multiple myeloma is a common and serious condition; however, the prognosis of multiple myeloma at the time of diagnosis remains unclear. METHOD: We conducted searches for literature in PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, and VIP databases up to 30 April 2023. Progression-free survival and overall survival with and without renal impairment at the time of multiple myeloma diagnosis were compared, and prognostic indicators were analysed. RESULTS: Six studies were finally included. Among patients with multiple myeloma, 319 had renal impairment, and 1166 had no renal impairment. Compared to the control group, no significant difference was observed in overall or progression-free survival in patients with multiple myeloma complicated with renal impairment. CONCLUSION: The limited low-quality evidence available does not support an association between prognosis and multiple myeloma complicated by kidney injury.

Diagnostic Efficacy and Safety of Low-Contrast-Dose Dual-Energy CT in Patients With Renal Impairment Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVE: This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function. MATERIALS AND METHODS: A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed. RESULTS: Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR (P < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration. CONCLUSION: Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.

Clinical and economic burden of medicare beneficiaries with multiple myeloma and renal impairment: An observational study.

Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This retrospective study aimed to generate an updated comprehensive assessment of the clinical and economic outcomes of MM patients with RI using the Medicare research identifiable files data with Part D linkage, which might assist in assessing the total clinical and socioeconomic burden of these high-risk and challenging-to-treat patients. Treatment patterns and clinical and economic outcomes in first line (1L) to fourth line (4L) therapy were described in Medicare beneficiaries (2012 to 2018) for MM patients with RI (RI MM cohort). For reference purposes, information on a general cohort of MM patients was generated and reported to highlight the clinical and economic burden of RI. Since the goal was to describe the burden of these patients, this study was not designed as a comparison between the 2 cohorts. Compared with the general MM cohort (n = 13,573), RI MM patients (24.9%) presented high MM-associated comorbidities. In the RI MM cohort, bortezomib-dexamethasone (45.7%), bortezomib-lenalidomide (18.6%), lenalidomide (12.3%), and bortezomib-cyclophosphamide (12.1%) were the most prevalent regimens in 1L; carfilzomib and pomalidomide were mostly received in 3L to 4L; and daratumumab in 4L. Across 1L to 4L, the RI MM cohort presented shorter median real-world progression-free survival (1L: 12.9 and 16.4 months) and overall survival (1L: 31.1 and 46.8 months) and higher all-cause healthcare resource utilization (1L incidence rate of inpatient days: 12.1 and 7.8 per person per year) than the general MM cohort. In the RI MM cohort, the mean all-cause total cost increased from 1L to 4L ($14,549-$18,667 per person per month) and was higher than that of the general MM cohort. RI MM patients presented higher clinical and economic burdens across 1L to 4L than the general MM patients in real-world clinical practice.

Host and fungal factors both contribute to cryptococcosis-associated hyperammonemia (cryptammonia).

Cryptococcus neoformans and Cryptococcus gattii are both known urease producers and have the potential to cause hyperammonemia. We hypothesized that the risk of hyperammonemia is increased by renal failure, burden of cryptococcal infection, and fungal strain characteristics. We performed a retrospective review of plasma ammonia levels in patients with cryptococcal infections. Risk factors for hyperammonemia were statistically compared between patients with and without hyperammonemia (>53 µmol/L). Cryptococcal cells from three patients included in the study were recovered from our biorepository. Strain characteristics including urease activity, ammonia production, growth curves, microscopy, melanin production, and M13 molecular typing were analyzed and compared with a wild-type (WT) C. neoformans strain. We included 29 patients, of whom 37.9% had hyperammonemia, 59% had disseminated cryptococcal infection (DCI), and 41% had isolated central nervous system infection. Thirty-eight percent of patients had renal failure and 28% had liver disease. Renal failure was associated with 4.4 times (95% confidence interval [CI] 1.5, 13.0) higher risk of hyperammonemia. This risk was higher in DCIs (RR 6.2, 95% CI 1.0, 40.2) versus isolated cryptococcal meningitis (RR 2.5, 95% CI, 0.40, 16.0). Liver disease and cryptococcal titers were not associated with hyperammonemia. C. neoformans from one patient with extreme hyperammonemia demonstrated a 4- to 5-fold increase in extracellular urease activity, slow growth, enlarged cell size phenotypes, and diminished virulence factors. Hyperammonemia was strongly associated with renal failure in individuals with DCI, surpassing associations with liver failure or cryptococcal titers. However, profound hyperammonemia in one patient was attributable to high levels of urease secretion unique to that cryptococcal strain. Prospective studies are crucial to exploring the significance of this association.IMPORTANCECryptococcus produces and secretes the urease enzyme to facilitate its colonization of the host. Urease breaks down urea into ammonia, overwhelming the liver's detoxification process and leading to hyperammonemia in some hosts. This underrecognized complication exacerbates organ dysfunction alongside the infection. Our study investigated this intricate relationship, uncovering a strong association between the development of hyperammonemia and renal failure in patients with cryptococcal infections, particularly those with disseminated infections. We also explore mechanisms underlying increased urease activity, specifically in strains associated with extreme hyperammonemia. Our discoveries provide a foundation for advancing research into cryptococcal metabolism and identifying therapeutic targets to enhance patient outcomes.

Simulating Healthy Participant Pharmacokinetics for Renal and Hepatic Impairment Studies: Retrospective Assessment of the Approach.

The recruitment of a parallel, healthy participants (HPs) arm in renal and hepatic impairment (RI and HI) studies is a common strategy to assess differences in pharmacokinetics. Limitations in this approach include the underpowered estimate of exposure differences and the use of the drug in a population for which there is no benefit. Recently, a method was published by Purohit et. al. (2023) that leveraged prior population pharmacokinetic (PopPK) modeling-based simulation to infer the distribution of exposure ratios between the RI/HI arms and HPs. The approach was successful, but it was a single example with a robust model having several iterations of development and fitting to extensive HP data. To test in more studies and models at different stages of development, our catalogue of RI/HI studies was searched, and those with suitable properties and from programs with available models were analyzed with the simulation approach. There were 9 studies included in the analysis. Most studies were associated with models that would have been available at the time (ATT) of the study, and all had a current, final model. For 3 studies, the HP PK was not predicted well by the ATT (2) or final (1) models. In comparison to conventional analysis of variance (ANOVA), the simulation approach provided similar point estimates and confidence intervals of exposure ratios. This PopPK based approach can be considered as a method of choice in situations where the simulation of HP data would not be an extrapolation, and when no other complicating factors are present.

Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency.

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of ß-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.

Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center.

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.

A mendelian randomization study revealing that metabolic syndrome is causally related to renal failure.

Background: The onset and progression of chronic kidney disease (CKD) has been linked to metabolic syndrome (MetS), with the results of recent observational studies supporting a potential link between renal failure and MetS. The causal nature of this relationship, however, remains uncertain. This study thus leveraged a Mendelian Randomization (MR) approach to probe the causal link of MetS with renal failure. Methods: A genetic database was initially used to identify SNPs associated with MetS and components thereof, after which causality was evaluated through the inverse variance weighted (IVW), MR-Egger regression, and weighted media techniques. Results were subsequently validated through sensitivity analyses. Results: IVW (OR = 1.48, 95% CI = 1.21-1.82, P =1.60E-04) and weighted median (OR = 1.58, 95% CI =1.15-2.17, P = 4.64E-03) analyses revealed that MetS was linked to an elevated risk of renal failure. When evaluating the specific components of MetS, waist circumference was found to be causally related to renal failure using the IVW (OR= 1.58, 95% CI = 1.39-1.81, P = 1.74e-11), MR-Egger (OR= 1.54, 95% CI = 1.03-2.29, P = 0.036), and weighted median (OR= 1.82, 95% CI = 1.48-2.24, P = 1.17e-8). The IVW method also revealed a causal association of hypertension with renal failure (OR= 1.95, 95% CI = 1.34-2.86, P = 5.42e-04), while renal failure was not causally related to fasting blood glucose, triglyceride levels, or HDL-C levels. Conclusion: These data offer further support for the existence of a causal association of MetS with kidney failure. It is thus vital that MetS be effectively managed in patients with CKD in clinical settings, particularly for patients with hypertension or a high waist circumference who are obese. Adequate interventions in these patient populations have the potential to prevent or delay the development of renal failure.

Age, Renal Failure and Transfusion are Risk Predictors of Prolonged Hospital Stay after Coronary Artery Bypass Grafting Surgery. / Idade, Insuficiência Renal e Transfusão são Preditores de Risco de Longa Permanência Hospitalar após Cirurgia de Revascularização do Miocárdio.

BACKGROUND: Identifying risk factors in cardiovascular surgery assists in predictability, resulting in optimization of outcomes and cost reduction. OBJECTIVE: This study aimed to identify preoperative and intraoperative risk predictors for prolonged hospitalization after coronary artery bypass grafting (CABG) surgery in the state of São Paulo, Brazil. METHODS: A cross-sectional analysis using data from the REPLICCAR II database, a prospective, consecutive, multicenter registry that included CABG surgeries performed between August 2017 and July 2019. The primary outcome was a prolonged hospital stay (PHS), defined as a postoperative period exceeding 14 days. Univariate and multivariate logistic regression analyses were performed to identify the predictors with significance set at p <0.05. RESULTS: The median age was 63 (57-70) years and 26.55% of patients were female. Among the 3703 patients analyzed, 228 (6.16%) had a PHS after CABG, with a median hospital stay of 17 (16-20) days. Predictors of PHS after CABG included age >60 years (OR 2.05; 95% CI 1.43-2.87; p<0.001); renal failure (OR 1.73; 95% CI 1.29-2.32; p <0.001) and intraoperative red blood cell transfusion (OR 1.32; 95% CI 1.07-2.06; p=0.01). CONCLUSION: Age >60 years, renal failure, and intraoperative red blood cell transfusion were independent predictors of PHS after CABG. The identification of these variables can help in multiprofessional strategic planning aimed to enhance results and resource utilization in the state of São Paulo.

FUNDAMENTO: A identificação de fatores de riscos na cirurgia cardiovascular auxilia na previsibilidade resultando na otimização de desfechos e redução de custos. OBJETIVO: Identificação dos preditores de risco pré e intraoperatórios para internação prolongada após cirurgia de revascularização do miocárdio (CRM) no Estado de São Paulo. MÉTODOS: Análise transversal no banco de dados REPLICCAR II, registro prospectivo, consecutivo, multicêntrico que incluiu cirurgias de revascularização miocárdica realizadas entre agosto de 2017 e julho de 2019. O desfecho principal foi o tempo de internação prolongado, definida como período de pós-operatório superior a 14 (quatorze) dias. Para a identificação dos preditores foram realizadas análises de regressão logística uni- e multivariada. Os valores de p menores de 0,05 foram considerados significativos. RESULTADOS: A mediana de idade foi de 63 (57-70) anos e 26,55% eram do sexo feminino. Dos 3703 pacientes analisados, 228 (6,16%) apresentaram longa permanência hospitalar (LPH) após a CRM e a mediana da internação foi de 17 (16-20) dias. Foram preditores da LPH após a CRM: idade >60 anos (OR 2,05; IC95% 1,43 - 2,87; p<0,001); insuficiência renal (OR 1,73; IC95% 1,29 - 2,32; p<0,001) e transfusão de hemácias no intraoperatório (OR 1,32; IC 1,07 - 2,06; p=0,01). CONCLUSÃO: Nesta análise, a idade > 60 anos, insuficiência renal e a transfusão de hemácias no intraoperatório foram preditores independentes de LPH após a CRM. A identificação destas variáveis pode ajudar no planejamento estratégico multiprofissional visando melhoria de resultados e otimização de recursos no estado de São Paulo.

Not only Van Gogh: a case of BRASH syndrome with concomitant digoxin toxicity.

BACKGROUND: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia. It constitutes a vicious circle in which the accumulation of pharmacologically active compounds and hyperkalemia lead to hemodynamic instability and heart failure. CASE PRESENTATION: A 66-year-old Caucasian female patient was admitted to the emergency department presenting with fatigue and bradycardia. Upon examination, the patient was found to be anuric and hypotensive. Laboratory investigations revealed metabolic acidosis and hyperkalemia. Clinical evaluation suggested signs of digoxin toxicity, with serum digoxin concentrations persistently elevated over several days. Despite the implementation of antikalemic measures, the patient's condition remained refractory, necessitating renal dialysis and administration of digoxin immune fab. CONCLUSION: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a life-threatening condition that requires prompt management. It is important to also consider potential coexisting clinical manifestations indicative of intoxication from other pharmacological agents. Specifically, symptoms associated with the accumulation of drugs eliminated via the kidneys, such as digoxin. These manifestations may warrant targeted therapeutic measures.

Favipiravir pharmacokinetics in COVID-19 patients with moderate to severe kidney dysfunction: Lessons learned.

OBJECTIVE: There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney dysfunction. The aim was to determine favipiravir pharmacokinetics (oral, 1,600 mg, q12h on day 1, then 600 mg, q12h for 4 days) in critically ill COVID-19 patients with kidney dysfunction and to compare those with observations reported in healthy adults. MATERIALS AND METHODS: In a descriptive study, blood samples taken from patients meeting the relevant criteria (estimated glomerular filtration rate < 60 mL/min) were collected and analyzed. Analysis of blood samples was done by high performance liquid chromatography (HPLC), and the maximal concentration (Cmax), the time of maximal concentration (tmax), half-life (T1/2) and area under the curve (AUC0-12h) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration. RESULTS: Based on analysis of samples collected in 7 patients, the Cmax (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T1/2 (5.8 vs. 4.8 hours) longer, tmax delayed, while total exposure was lower (AUC0-12: 192.53 vs. 446.09 µg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5. CONCLUSION: In patients with kidney dysfunction related to COVID-19, favipiravir did not reach the expected exposure. This may be due to poorer and delayed absorption, and subsequent altered disposition. Population pharmacokinetic and mechanistic studies are needed to better explore the relevant covariates and to determine the optimal dose in these patients, as this drug is likely of relevance for other indications.

Association of Renal Impairment with Clinical Outcomes Following Endovascular Therapy in Acute Basilar Artery Occlusion.

Purpose: Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association of RI with clinical outcomes in patients with acute basilar artery occlusion (ABAO), and the impact of RI on the effects of endovascular therapy (EVT) versus standard medical treatment (SMT). Patients and Methods: We used data from the BASILAR registry, an observational, prospective, nationwide study of patients with ABAO in routine clinical practice in China. Baseline estimated glomerular filtration rate (eGFR) was recorded at admission. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included favourable outcome (mRS score 0-3), mortality, and symptomatic intracranial haemorrhage (sICH). Multivariate logistic regression was used to assess the association of RI with mortality and functional improvement at 90 days. Results: Among 829 patients enrolled, 747 patients were analysed. The median baseline eGFR was 89 mL/min/1.73m2 (IQR, 71-100), and 350 (46.8%), 297 (39.8%), and 100 (13.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73m2, respectively. RI was associated with increased mortality (adjusted odds ratio [aOR], 1.97; 95% CI, 1.15-3.67) at 90 days and decreased survival probability (aOR 1.74; 95% CI, 1.30-2.33) within 1 year. EVT was associated with better functional improvement (common aOR, 2.50; 95% CI, 1.43-4.35), favourable outcome (aOR 5.42; 95% CI, 1.92-15.29) and lower mortality (aOR 0.47; 95% CI, 0.25-0.88) in ABAO patients with eGFR ≥90 mL/min/1.73m2. However, RI was not modified the relationship of EVT with functional improvement (common aOR, 3.03; 95% CI, 0.81-11.11), favourable outcome (aOR 2.10; 95% CI, 0.45-9.79), and mortality (aOR 0.56; 95% CI, 0.15-2.06) by eGFR categories. Conclusion: RI is associated with reduced efficacy of EVT and worse functional outcome and higher mortality at 3 months and lower survival probability at 1 year in patients with ABAO.

Prevalence of renal insufficiency and factors associated among selected cancer patients on chemotherapy at Ocean Road Cancer Institute in Tanzania: a cross-sectional study.

BACKGROUND: Cancer is among the leading cause of death worldwide. Chemotherapy is commonly used in cancer management and among the challenges in managing cancer patients is renal insufficiency (RI), which can be due to cancer or anticancer treatment and can be potentiated by different factors. Data regarding the prevalence of RI and associated factors in Tanzania is scanty. This study aims to assess the prevalence of RI and associated factors among selected cancer patients on chemotherapy. METHODS: This analytical cross-sectional study was conducted at Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania, from March to May 2023. The study included cancer patients on chemotherapy. Data was collected using semi-structured questionnaires whereby socio-demographics, clinical and laboratory data were recorded. Data was analyzed by using STATA version 15. Categorical data was presented as frequencies and percentages, and continuous data was summarized using means. A modified Poisson regression model was used to assess factors associated with RI. The p-values ≤ 0.05 was considered statistically significant. RESULTS: Out of 354 patients, the majority (76.6%) were female. The enrolled patients' mean age was 53 ± 13.19 years. The proportion of cancer patients with RI was 62.2% with most (60%) having stage 2 and stage 3 (37.7%). Age, hypertension (HTN), human immunodeficiency virus (HIV), diabetes mellitus (DM) and non-steroidal anti-inflammatory drugs (NSAIDs) use were significantly associated with increased risk of RI (p ≤ 0.05). CONCLUSION: This study showed that RI is common among cancer patients on chemotherapy. Age, HTN, DM, HIV and NSAIDS use were associated with RI. Close monitoring of kidney function is necessary for cancer patients with other factors associated with RI. Use of creatinine clearance (CrCl) rather than serum creatinine in estimating kidney function is important.

[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. METHODS AND RESULTS: We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all-cause death using adjusted time-to-event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person-years (95% CI, 231-233), with a higher rate in women than in men (248 per thousand person-years [95% CI, 247-250] versus 219 per thousand person-years [95% CI, 217-220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13-1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15-1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28-1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99-1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88-0.90]) and a lower risk of all-cause death than men (HR, 0.96 [95% CI, 0.95-0.97]). CONCLUSIONS: Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality.

Kidney Failure in Pauci-immune Crescentic Glomerulonephritis: Rationale for Immunosuppression to Improve Kidney Outcome.

PURPOSE OF REVIEW: Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis. RECENT FINDINGS: Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management.