Mass Spectrometry-Based Lipidomics Reveals Differential Changes in the Accumulated Lipid Classes in Chronic Kidney Disease

Chronic kidney disease (CKD) is characterized by the progressive loss of functional nephrons. Although cardiovascular disease (CVD) complications and atherosclerosis are the leading causes of morbidity and mortality in CKD, the mechanism by which the progression of CVD accelerates remains unclear. To reveal the molecular mechanisms associated with atherosclerosis linked to CKD, we applied a shotgun lipidomics approach fortified with standard laboratory analytical methods and gas chromatography-mass spectrometry technique on selected lipid components and precursors to analyze the plasma lipidome in CKD and classical CVD patients. The MS-based lipidome profiling revealed the upregulation of triacylglycerols in CKD and downregulation of cholesterol/cholesteryl esters, sphingomyelins, phosphatidylcholines, phosphatidylethanolamines and ceramides as compared to CVD group and controls. We have further observed a decreased abundance of seven fatty acids in CKD with strong inter-correlation. In contrast, the level of glycerol was elevated in CKD in comparison to all analyzed groups. Our results revealed the putative existence of a functional causative link—the low cholesterol level correlated with lower estimated glomerular filtration rate and kidney dysfunction that supports the postulated “reverse epidemiology” theory and suggest that the lipidomic background of atherosclerosis-related to CKD is unique and might be associated with other cellular factors, i.e., inflammation.

Prevalence of malnutrition inflammation complex syndrome among patients on maintenance haemodialysis at Muhimbili National Hospital in Tanzania: a cross-sectional study

Background Malnutrition, inflammation, and the combination thereof are predictors of poor outcomes in haemodialysis patients. Malnutrition Inflammation Complex Syndrome (MICS) is an accelerator of atherosclerosis and portends high mortality. Early recognition and treatment of MICS may help to improve the clinical outlook of such patients. This study investigated the prevalence of MICS and its associated factors among patients on maintenance haemodialysis at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. Methods This was a prospective cross-sectional observational study done among 160 adult patients on maintenance haemodialysis at MNH in 2019. All participants provided written informed consent. Questionnaires were used to collect data and patients’ blood was tested for complete blood count (CBC), C-reactive protein (CRP), ferritin, transferrin, creatinine, urea, total cholesterol, and albumin. The Malnutrition Inflammation Score was used to assess MICS and its severity. Data analysis was done using the SPSS 20 software. Results Of the 160 patients included in the study, 111 (69.4%) were male. The mean age (±SD) of patients and mean duration (±SD) on haemodialysis were 52.2(13.3) years and 22(18) months respectively. MICS was prevalent in 46.3% (mild in 24.4% and moderate to severe in 21.9%). Long-term haemodialysis (> 4 years) was an independent predictor of MICS [Adjusted Odds Ratio, AOR 5.04 (95% CI: 1.33–19.2), p < 0.05]. Hypercholesterolaemia was a negative predictor of MICS [AOR 0.11 (95% CI: 0.01–0.97), p < 0.05]. Patients with MICS had significantly lower mean body mass index, serum albumin, total cholesterol, transferrin, haemoglobin, and creatinine levels. The presence of MICS was higher in underweight patients and those who had inflammation. Haemodialysis adequacy did not correlate with MICS. Conclusion Malnutrition Inflammation Complex Syndrome is relatively common among patients on haemodialysis in Dar es Salaam, Tanzania. Our study has shown a longer duration on haemodialysis to be associated with the occurrence of MICS; on the contrary, having hypercholesterolaemia seems to be protective against MICS consistent with the concept of reverse epidemiology. Patients on haemodialysis should be assessed regularly for malnutrition and inflammation and should receive appropriate and timely treatment to reduce the burden of associated morbidity, and mortality to these patients.

Prevalence of Malnutrition Inflammation Complex Syndrome among Patients on Maintenance Haemodialysis at Muhimbili National Hospital in Tanzania: A Cross-Sectional Study

Background: Malnutrition, inflammation, and the combination thereof are predictors of poor outcomes in haemodialysis patients. Malnutrition Inflammation Complex Syndrome (MICS) is an accelerator of atherosclerosis and portends high mortality. Early recognition and treatment of MICS may help to improve the clinical outlook of such patients. This study investigated the prevalence of MICS and its associated factors among patients on maintenance haemodialysis at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. Methods: This was a prospective cross-sectional observational study done among 160 adult patients on maintenance haemodialysis at MNH in 2019. All participants provided written informed consent. Questionnaires were used to collect data and patients’ blood was tested for complete blood count (CBC), C-reactive protein (CRP), ferritin, transferrin, creatinine, urea, total cholesterol, and albumin. The Malnutrition Inflammation Score was used to assess MICS and its severity. Data analysis was done using the SPSS 20 software. Results: Of the 160 patients included in the study, 111 (69.4%) were male. The mean age (±SD) of patients and mean duration (±SD) on haemodialysis were 52.2(13.3) years and 22(18) months respectively. MICS was prevalent in 46.3% (mild in 24.4% and moderate to severe in 21.9%). Long-term haemodialysis (>4years) was an independent predictor of MICS [Adjusted Odds Ratio, AOR 5.04 (95% CI: 1.33–19.2), p<0.05]. Hypercholesterolaemia was a negative predictor of MICS [AOR 0.11 (95% CI: 0.01-0.97), p<0.05]. Patients with MICS had significantly lower mean body mass index, serum albumin, total cholesterol, transferrin, haemoglobin, and creatinine levels. The presence of MICS was higher in underweight patients and those who had inflammation. Haemodialysis adequacy did not correlate with MICS. Conclusion: Malnutrition Inflammation Complex Syndrome is relatively common among patients on haemodialysis in Dar es Salaam, Tanzania. Our study has shown a longer duration on haemodialysis to be associated with the occurrence of MICS; on the contrary, having hypercholesterolaemia seems to be protective against MICS consistent with the concept of reverse epidemiology. Patients on haemodialysis should be assessed regularly for malnutrition and inflammation and should receive appropriate and timely treatment to reduce the burden of associated morbidity, and mortality to these patients.

Prevalence of Malnutrition Inflammation Complex Syndrome among Patients on Maintenance Haemodialysis at Muhimbili National Hospital in Tanzania: A Cross-Sectional Study

Background: Malnutrition, inflammation, and combination thereof are predictors of poor outcomes in haemodialysis patients. Malnutrition Inflammation Complex Syndrome (MICS) is an accelerator of atherosclerosis and portends high mortality. Early recognition and treatment of MICS may help to improve the clinical outlook of such patients. This study investigated the prevalence of MICS and its associated factors among patients on maintenance haemodialysis at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. Methods: This was a prospective cross-sectional observational study done among 160 adult patients on maintenance haemodialysis at MNH in 2019. All participants provided written informed consent. Questionnaires were used to collect data and patients’ blood was tested for complete blood count (CBC), C-reactive protein (CRP), ferritin, transferrin, creatinine, urea, total cholesterol, and albumin. The Malnutrition Inflammation Score was used to assess MICS and its severity. Data analysis was done using the SPSS 20 software.Results: Of the 160 patients included in the study, 111 (69.4%) were male. The mean age (±SD) of patients and mean duration (±SD) on haemodialysis were 52.2(13.3) years and 22(18) months respectively. MICS was prevalent in 46.3% (mild in 24.4% and moderate to severe in 21.9%). Long-term haemodialysis (>4years) was an independent predictor of MICS [Adjusted Odds Ratio, AOR 5.04 (95% CI: 1.33–19.2), p<0.05]. Hypercholesterolaemia was a negative predictor of MICS [AOR 0.11 (95% CI: 0.01-0.97), p<0.05]. Patients with MICS had significantly lower mean body mass index, albumin, total cholesterol, transferrin, haemoglobin and serum creatinine levels. The presence of MICS was higher in underweight patients and those who had inflammation. Haemodialysis adequacy did not correlate with MICS.Conclusion: Malnutrition Inflammation Complex Syndrome is relatively common among patients on haemodialysis in Dar es Salaam, Tanzania. Our study has shown a longer duration on haemodialysis to be associated with the occurrence of MICS; on the contrary, having hypercholesterolaemia seems to be protective against MICS consistent with the concept of reverse epidemiology. Patients on haemodialysis should be assessed regularly and accordingly treated for malnutrition and inflammation which if left unattended, compounds morbidity, and mortality among these patients.

Sodium Intake and Chronic Kidney Disease

In Chronic Kidney Disease (CKD) patients, elevated blood pressure (BP) is a frequent finding and is traditionally considered a direct consequence of their sodium sensitivity. Indeed, sodium and fluid retention, causing hypervolemia, leads to the development of hypertension in CKD. On the other hand, in non-dialysis CKD patients, salt restriction reduces BP levels and enhances anti-proteinuric effect of renin–angiotensin–aldosterone system inhibitors in non-dialysis CKD patients. However, studies on the long-term effect of low salt diet (LSD) on cardio-renal prognosis showed controversial findings. The negative results might be the consequence of measurement bias (spot urine and/or single measurement), reverse epidemiology, as well as poor adherence to diet. In end-stage kidney disease (ESKD), dialysis remains the only effective means to remove dietary sodium intake. The mismatch between intake and removal of sodium leads to fluid overload, hypertension and left ventricular hypertrophy, therefore worsening the prognosis of ESKD patients. This imposes the implementation of a LSD in these patients, irrespective of the lack of trials proving the efficacy of this measure in these patients. LSD is, therefore, a rational and basic tool to correct fluid overload and hypertension in all CKD stages. The implementation of LSD should be personalized, similarly to diuretic treatment, keeping into account the volume status and true burden of hypertension evaluated by ambulatory BP monitoring.

Prevalence of Malnutrition Inflammation Complex Syndrome among Patients on Maintenance Haemodialysis in Tanzania: A Cross-Sectional Study

Background: Malnutrition, inflammation and combination thereof are predictors of poor outcomes in haemodialysis patients. Malnutrition Inflammation Complex Syndrome (MICS) is an accelerator of atherosclerosis and portends high mortality. Early recognition and treatment of MICS may help to improve the clinical outlook of such patients. This study investigated on the prevalence of MICS and its associated factors among patients on maintenance haemodialysis at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. Methods: This was a cross-sectional descriptive study done among 160 adult patients on maintenance haemodialysis at MNH in 2019. All participants provided written informed consent. Questionnaires were used to collect data and some laboratory investigations were done. The Malnutrition Inflammation Score was used to access MICS and its severity. Data analysis was done using the SPSS 20 software.Results: Of the 160 patients included in the study, 111 (69.4%) were male. The mean age (±SD) of patients and mean duration (±SD) on haemodialysis were 52.2(13.3) years and 22(18) months respectively. MICS was prevalent in 46.3% (mild in 24.4% and moderate to severe in 21.9%). Long-term haemodialysis (>4years) was an independent predictor of MICS [Adjusted Odds Ratio, AOR 5.04 (95% CI: 1.33–19.2), p<0.05]. Hypercholesterolaemia was a negative predictor of MICS [AOR 0.11 (95% CI: 0.01-0.97), p<0.05]. Patients with MICS had significantly lower mean body mass index, albumin, total cholesterol, transferrin, haemoglobin and serum creatinine levels. Nutritional status and inflammation significantly associated with MICS; adequacy of dialysis did not correlate with MICS.Conclusion: Malnutrition Inflammation Complex Syndrome is relatively common among patients on haemodialysis in Dar es Salaam, Tanzania. Our study has shown longer duration on haemodialysis to be associated with the occurrence of MICS; to the contrary, having hypercholesterolaemia seems to be protective against MICS rhyming well with the concept of reverse epidemiology. Patients on haemodialysis should to be regularly assessed and accordingly treated for malnutrition and inflammation which if left unattended, compounds morbidity and mortality among these patients.

Complexity and Non-Linearity of Cardiovascular Risk Factors in Older Patients With Multimorbidity and Reduced Renal Function

The aim of this study was to reveal the complex pathophysiology network that may underly associations between chronic kidney disease (CKD), defined with mildly to moderately decreased renal function, and increased CV risk. For this purpose, we used a set of parameters indicating biochemical disorders, known to be associated with CKD. This set of parameters was taken from the larger dataset, where clinical characteristics of older patients with multimorbidity (the existence of two or more chronic diseases at the same person) and mildly to moderately decreased renal function, have been described with multiple parameters. On the selected set of parameters, we applied Machine Learning (ML) methods, to demonstrate relationships between the parameters. We used SMOreg algorithm for developing regression model. At first, we applied the SMOreg algorithm on the dataset to predict C-reactive protein (CRP) and then we used same algorithm to discover pairwise nonlinear relationships between variables such as Age-fglu, Chol-HTC and HB-FE, Age-Homcis, Clear-Homcis, Homcis-TG, CRP-TG. The assessment of non-linear relationships among multiple parameters indicating confounding factors of renal function decline, in older people with multimorbidity, has revealed the close associations between insulin resistance and serum albumin and homocystein levels. Several hypotheses are arising from these study with the potential to facilitate research on the concept of the reverse epidemiology. Although this analytical approach is far from being sufficient to provide the full understanding of the relationships between cardiovascular risk factors and decreased renal function, in older population, by means of the reverse epidemiology, this study emphasizes a need for more integrated and dynamical approaches, when assessing these factors.

A Practical Approach to Nutrition, Protein-Energy Wasting, Sarcopenia, and Cachexia in Patients with Chronic Kidney Disease

Objectives of Review: Protein-energy wasting (PEW) is a state of disordered catabolism resulting from metabolic and nutritional derangements in chronic disease states. Patients with chronic kidney disease (CKD), and end-stage renal disease (ESRD) in particular, have muscle wasting, sarcopenia, and cachexia that contribute to frailty and morbidity. Moreover, reverse epidemiology findings have strongly linked PEW with mortality in CKD and ESRD. Updated Findings: The malnutrition-inflammation score (KALANTAR Score) provides a useful tool to predict nutritional risk. A stronger focus on renal nutrition in renal patients is needed to attenuate cachexia and muscle loss. Malnutrition is a far greater threat in patients with renal disease than obesity, which means dietary counseling needs to be tailored to reflect this observation. The need to achieve optimal caloric intake is compounded by the need to limit excess protein intake in CKD, resulting in the need for energy supplementation to avoid PEW. Preventing PEW is the most pressing clinical concern in CKD/ESRD. Other nutritional issues to reckon in renal disease include the need to normalize serum bicarbonate to manage acidosis, uric acid control, and phosphorous control in CKD and ESRD. Exercise maybe beneficial, but further work is needed to prove a conclusive benefit via a randomized trial. Summary: PEW prevention is an integral part of renal nutrition and is of paramount importance given the obesity paradox. Integrative approaches by physicians and dieticians are needed to take a holistic view of a patient’s diet beyond just control of particular laboratory parameters.