The role of obesity on chronic kidney disease development, progression, and cardiovascular complications

The complex links between obesity, chronic kidney disease (CKD) and cardiovascular disease (CVD) are not completely understood. The objective of this review is to describe and discuss the anatomy, physiology, and biochemistry of the adipose tissue, as well as its involvement in the pathophysiology of CVD and CKD. We searched for original articles in PubMed. The search terms used were “obesity”, “CKD”, and “CVD”. In addition, we also identified publications from our personal databases of literature about obesity, CKD and CVD to identify any important studies that might have been missing from the PubMed search. We further searched the reference lists of identified articles for further relevant papers. Epidemiological studies show that obesity is associated with obesity-related glomerulopathy (ORG) as well as an increase in the risk of CKD in the general population. A number of pathophysiological mechanisms, including renal hemodynamic changes, neurohumoral pathways that activate the sympathetic and renin-angiotensin-aldosterone systems, proinflammatory and profibrotic effects of various adipokines, and insulin resistance may explain the excessive risk of CKD development and progression in obese patients. In patients with mild to moderate CKD, obesity per se contributes a modest increase in cardiovascular risk, while the effect of obesity on the cardiovascular risk of patients with advanced CKD is probably due to the concurrent metabolic syndrome and coexisting cardiovascular risk factors, but the effect of obesity on the cardiovascular risk of patients with advanced CKD is probably the result of the concomitant metabolic syndrome and coexisting cardiovascular risk factors. There are recent data suggesting that subcutaneous and visceral adipose tissue have different and probably opposite effects on the CVD risk in CKD. Further studies are necessary to distinguish the specific clinical implication of different adipose tissue compartments, and to determine the principal mediators that connect obesity, CKD and CVD

Urinary and Kidney Podocalyxin and Podocin Levels in Diabetic Kidney Disease: A Kidney Biopsy StudyPlain-Language Summary

Rationale &amp; Objective: Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD. Study Design: Observational cohort. Setting &amp; Participants: 118 consecutive patients with biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls. Predictors: Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting. Outcomes: Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months. Analytical Approach: Correlation and time to event analysis. Results: Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level (r = 0.562, P < 0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82; P = 0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95; P = 0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline (r = 0.238, P = 0.01) but did not predict dialysis-free survival. Limitations: Small sample size; lack of serial measurement. Conclusions: Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use

Recombinant erythropoietin treatment improves serum podocyte marker levels in diabetic kidney disease

Background: Recombinant human erythropoietin (rHuEPO) is an effective treatment for renal anemia. Recently, there is evidence to suggest that rHuEPO may reduce podocyte injury in diabetic kidney disease (DKD). However, there is no published study on the change in podocyte injury marker levels before and after rHuEPO treatment in DKD. Methods: We measured serum nephrin and podocalyxin level, and their corresponding plasma mRNA levels, in 49 DKD patients before rHuEPO treatment, and then 12 and 36 weeks afterward. Results: There were reductions in serum nephrin (p = 0.002) and podocalyxin levels (p = 0.09), as well as their corresponding plasma mRNA levels (p < 0.0001 for both) after rHuEPO treatment. The change in serum nephrin and podocin level had significant inverse correlation with the concomitant change in hemoglobin level (r = −0.670 and −0.739 respectively, p < 0.0001 for both), but not with the change in kidney function or proteinuria. Conclusion: Serum nephrin and podocalyxin levels and their corresponding plasma mRNA levels were significant reduced after rHuEPO treatment in DKD patients, and the change in serum nephrin and podocalyxin levels correlated with the change in hemoglobin level. The effect of rHuEPO on podocyte injury deserves further study

Intra-renal and urinary glycogen synthase kinase 3 beta levels in diabetic and non-diabetic chronic kidney disease

Background Renal glycogen synthase kinase-3 beta (GSK3β) over-activity has been associated with a diverse range of kidney diseases. GSK3β activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intra-renal GSK3β levels in DKD and non-diabetic chronic kidney disease (CKD). Methods We recruited 118 consecutive biopsy-proved DKD patients and 115 non-diabetic CKD patients. Their urinary and intra-renal GSK3β levels were measured. They were then followed for dialysis-free survival and rate of renal function decline. Results DKD group had higher intra-renal and urinary GSK3β levels than non-diabetic CKD (p<0.0001 for both), but their urinary GSK3β mRNA levels were similar. Urinary p-GSK3β level is statisticsly significantly corretated with the baseline estimated glomerular filtration rate (eGFR), but urinary GSK3β level by ELISA, it mRNA level, the p-GSK3β level, or the p-GSK3β/GSK3β ratio had no association with dialysis-free survival or the slope of eGFR decline. In contrast, intra-renal pY216-GSK3/total GSK3 ratio significantly correlated with the slope of eGFR decline (r = -0.335, p = 0.006), and remained an independent predictor after adjusting for other clinical factors. Conclusion Intra-renal and urinary GSK3β levels were increased in DKD. Intra-renal pY216-GSK3/total GSK3 ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3β in kidney diseases deserve further studies

Dietary Micronutrient Intake and Its Relationship with the Malnutrition–Inflammation–Frailty Complex in Patients Undergoing Peritoneal Dialysis

Background: The relationship between dietary patterns and the malnutrition–inflammation–frailty complex in patients undergoing peritoneal dialysis (PD) is currently unknown. Our objective was to measure dietary nutrient intake and evaluate its association with malnutrition, inflammation, and frailty. Methods: We prospectively recruited adult PD patients. We assessed their dietary nutrient intake using a food frequency questionnaire. Frailty, malnutrition, and inflammation were evaluated by validated Frailty Score (FQ), Subjective Global Assessment (SGA), and Malnutrition-Inflammation Score (MIS). Results: A total of 209 patients were recruited for the study. Among them, 89 patients (42.6%) had an insufficient protein intake, and 104 patients (49.8%) had an insufficient energy intake. Additionally, 127 subjects were identified as frail, characterized by being older (61.9 ± 9.5 vs. 55.6 ± 12.8, p p p p p = 0.01), and MIS (r = −0.22, p = 0.01). In the multivariate model, a higher dietary zinc intake predicted a higher SGA (beta 0.03, p = 0.003) and lower FQ (beta −0.38, p p p = 0.009). Conclusion: Dietary inadequacy and micronutrient deficiency are common among the PD population. Dietary zinc intake is independently associated with an improved nutrition, physical condition, and reduced inflammatory state

Additional file 1 of Urinary podocyte stress marker as a prognostic indicator for diabetic kidney disease

Supplementary Material

Epidemiology and Outcomes of Hypernatraemia in Patients with COVID-19&mdash;A Territory-Wide Study in Hong Kong

Background: Dysnatraemias are commonly reported in COVID-19. However, the clinical epidemiology of hypernatraemia and its impact on clinical outcomes in relation to different variants of SARS-CoV-2, especially the prevailing Omicron variant, remain unclear. Methods: This was a territory-wide retrospective study to investigate the clinical epidemiology and outcomes of COVID-19 patients with hypernatraemia at presentation during the period from 1 January 2020 to 31 March 2022. The primary outcome was 30-day mortality. Key secondary outcomes included rates of hospitalization and ICU admission, and costs of hospitalization. Results: In this study, 53,415 adult COVID-19 patients were included for analysis. Hypernatraemia was observed in 2688 (5.0%) patients at presentation, of which most cases (99.2%) occurred during the local &ldquo;5th wave&rdquo; dominated by the Omicron BA.2 variant. Risk factors for hypernatraemia at presentation included age, institutionalization, congestive heart failure, dementia, higher SARS-CoV-2 Ct value, white cell count, C-reactive protein and lower eGFR and albumin levels (p &lt; 0.001 for all). Patients with hypernatraemia showed significantly higher 30-day mortality (32.0% vs. 5.7%, p &lt; 0.001) and longer lengths of stay (12.9 &plusmn; 10.9 vs. 11.5 &plusmn; 12.1 days, p &lt; 0.001) compared with those with normonatraemia. Multivariate analysis revealed hypernatraemia at presentation as an independent predictor for 30-day mortality (aHR 1.32, 95% CI 1.14&ndash;1.53, p &lt; 0.001) and prolonged hospital stays (OR 1.55, 95% CI 1.17&ndash;2.05, p = 0.002). Conclusions: Hypernatraemia is common among COVID-19 patients, especially among institutionalized older adults with cognitive impairment and other comorbidities during large-scale outbreaks during the Omicron era. Hypernatraemia is associated with unfavourable outcomes and increased healthcare utilization

Omentin-1 Levels and Outcomes in Incident Peritoneal Dialysis PatientsPlain-Language summary

Rationale &amp; Objective: Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients. Study Design: Retrospective analysis of prospective cohort. Setting &amp; Participants: 152 incident PD patients. Predictors: Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression. Outcomes: Patient survival, technique survival, hospital admission, and duration of stay. Analytical Approach: Time-to-event survival analyses; linear regression for hospitalization. Results: The mean age was 58.4 ± 11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival (P = 0.92) or technique survival (P = 0.83) but had a modest correlation with a lower number of hospital admissions (P = 0.07) and shorter duration of hospital stay (P = 0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (β, -0.13; 95% CI, -0.26 to -0.002; P = 0.05) and shorter hospitalization duration (β, -0.20; 95% CI, -0.38 to -0.02; P = 0.03). Limitations: Observational study with baseline measures only. Conclusions: Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients

The Impact of Volume Overload on the Longitudinal Change of Adipose and Lean Tissue Mass in Incident Chinese Peritoneal Dialysis Patients

Patients treated with peritoneal dialysis (PD) experience complex body composition changes that are not adequately reflected by traditional anthropometric parameters. While lean and adipose tissue mass can be readily assessed by bioimpedance spectroscopy (BIS), there is concern about the potential confounding effect of volume overload on these measurements. This study aimed to assess the influence of fluid status (by echocardiography) on body composition parameters measured by BIS and to describe the longitudinal changes in adipose and lean tissue mass. We conducted a prospective observational study in a tertiary hospital. Incident Chinese PD patients underwent baseline echocardiography and repeated BIS measurements at baseline and 12 months later. Among 101 PD patients, lean tissue index (LTI) or fat tissue index (FTI) was not associated with echocardiographic parameters that reflected left ventricular filling pressure (surrogate of volume status). Sixty-eight patients with repeated BIS had a significant increase in body weight and FTI, while LTI remained similar. Gains in fat mass were significantly associated with muscle wasting (beta = −0.71, p p < 0.0001) but not LTI. Body composition assessments by BIS were not affected by fluid status and should be considered as part of comprehensive nutrition assessment in PD patients

Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57–3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08–2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80–13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13–12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006–0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02–0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35–50.5, p = 0.02). Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD