Changes in cerebral oxygenation and cerebral blood flow during hemodialysis - A simultaneous near-infrared spectroscopy and positron emission tomography study

Near-infrared spectroscopy (NIRS) is used to monitor cerebral tissue oxygenation (rSO2) depending on cerebral blood flow (CBF), cerebral blood volume and blood oxygen content. We explored whether NIRS might be a more easy applicable proxy to [15O]H2O positron emission tomography (PET) for detecting CBF changes during hemodialysis. Furthermore, we compared potential determinants of rSO2 and CBF. In 12 patients aged ≥ 65 years, NIRS and PET were performed simultaneously: before (T1), early after start (T2), and at the end of hemodialysis (T3). Between T1 and T3, the relative change in frontal rSO2 (ΔrSO2) was -8 ± 9% ( P = 0.001) and -5 ± 11% ( P = 0.08), whereas the relative change in frontal gray matter CBF (ΔCBF) was -11 ± 18% ( P = 0.009) and -12 ± 16% ( P = 0.007) for the left and right hemisphere, respectively. ΔrSO2 and ΔCBF were weakly correlated for the left (ρ 0.31, P = 0.4), and moderately correlated for the right (ρ 0.69, P = 0.03) hemisphere. The Bland-Altman plot suggested underestimation of ΔCBF by NIRS. Divergent associations of pH, pCO2 and arterial oxygen content with rSO2 were found compared to corresponding associations with CBF. In conclusion, NIRS could be a proxy to PET to detect intradialytic CBF changes, although NIRS and PET capture different physiological parameters of the brain

Brain dysfunction in tubular and tubulointerstitial kidney diseases

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research

An acute rise of plasma Na+ concentration associates with syndecan-1 shedding during hemodialysis

An acute rise of plasma Na+ concentration associates with syndecan-1 shedding during hemodialysis. Am J Physiol Renal Physiol 319: F171-F177, 2020. First published June 15, 2020; doi:10.1152/ajprenal.00005.2020.-Endothelial dysfunction (ED) contributes to the high incidence of cardiovascular events in patients undergoing hemodialysis. Syndecan-1 in the endothelial glycocalyx can be shed into the circulation, serving as a biomarker for ED. As Na+ is a trigger for glycocalyx shedding, we now tested whether hemodialysis, with higher dialysate Na+ concentrations, is associated with more syndecan-1 shedding compared with standard hemodialysis (SHD). In this crossover study in 29 patients, plasma syndecan-1 was repeatedly measured during SHD and during Hemocontrol hemodialysis (HHD), which is characterized by initially higher dialysate and plasma Na+ levels. Courses of syndecan-1 were compared with linear mixed models. Syndecan-1 shedding was assessed by area under the curve analysis. Plasma Na+ increased early after the start of SHD and HHD, with higher values during HHD (30 min: 142.3 vs. 139.9 mM, P < 0.001). Syndecan-1 increased significantly during both conditions, but the percent change was higher (42.9% vs. 19.5%) and occurred earlier (120 vs. 180 min) during HHD. Syndecan-1 levels were significantly higher at 120 min during HHD compared with SHD (P < 0.05). Overall, syndecan-1 shedding was higher during HHD compared with SHD (means: 40.4 vs. 19.0 arbitrary units, P = 0.06). Lower predialysis plasma Na+ and osmolality were associated with greater intradialytic increases in syndecan-1 levels (both groups, P = 0.001). The rise in plasma syndecan-1 levels was more pronounced and occurred earlier during hemodialysis with higher plasma Na+ levels. Although we cannot prove that the rise in plasma syndecan-1 originates from the endothelial glycocalyx, our findings are compatible with Na+-driven endothelial glycocalyxderived syndecan-1 shedding

The Tryptophan-Kynurenine Pathway, Systemic Inflammation, and Long-Term Outcome after Kidney Transplantation

BACKGROUND: Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine, and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest in this pathway, because of its pro-inflammatory nature, and drugs interfering in it receive increasing attention. We aimed to investigate whether serum and urinary parameters of the tryptophan-kynurenine pathway, and particularly cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long-term outcome in renal transplant recipients (RTR). METHODS: Data were collected in outpatient RTR with a functioning graft for >1 year. Tryptophan, kynurenine and 3-hydroxykynurenine in serum and urine were measured using LC-MS/MS. RESULTS: A total of 561 RTR (age 51±12 years; 56% male) were included at median 6.0 [2.6-11.6] years post-transplantation. Baseline median serum tryptophan was 40.0 [34.5-46.0] µmol/l; serum kynurenine was 1.8 [1.4-2.2] µmol/l; serum 3-hydroxykynurenine was 42.2 [31.0-61.7] nmol/l. Serum kynurenine and 3-hydroxykynurenine were strongly associated with parameters of systemic inflammation. During follow-up for 7.0 [6.2-7.5] years, 51 RTR (9%) developed graft failure and 120 RTR (21%) died. Both serum kynurenine and 3-hydroxykynurenine were independently associated with graft failure (HR 1.72 [1.23-2.41], P=0.002 and HR 2.03 [1.42-2.90], P<0.001). Serum 3-hydroxykynurenine was also independently associated with mortality (HR 1.37 [1.08-1.73], P=0.01), while serum kynurenine was not. Urinary tryptophan-kynurenine pathway parameters were not associated with outcome. CONCLUSIONS: Of tryptophan metabolites, serum 3-hydroxykynurenine is cross-sectionally most strongly and consistently associated with systemic inflammation and prospectively with adverse long-term outcome after kidney transplantation. Serum 3-hydroxykynurenine may be an interesting biomarker and target for the evaluation of drugs interfering in the tryptophan-kynurenine pathway

Clinical triage of patients on kidney replacement therapy presenting with COVID-19: an ERACODA registry analysis.

BackgroundPatients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes.MethodsThe European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage.ResultsAmong 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage.ConclusionsThis study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic

Effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and left ventricular function assessed with 13N-NH3 PET and echocardiography

Hemodialysis is associated with a fall in myocardial perfusion and may induce regional left ventricular (LV) systolic dysfunction. The pathophysiology of this entity is incompletely understood and the contribution of ultrafiltration and diffusive dialysis has not been studied. We investigated the effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and LV function. Eight patients (7 male, age 55±18 years) underwent 60 min of isolated ultrafiltration and 60 min of isovolemic dialysis in randomized order. Myocardial perfusion was assessed by 13N-NH3 PET before and at the end of treatment. LV systolic function was assessed by echocardiography. Regional LV systolic dysfunction was defined as an increase in wall motion score in ≥2 segments. Isolated ultrafiltration (ultrafiltration rate 13.6±3.9 ml/kg/h) induced hypovolemia whereas isovolemic dialysis did not (blood volume change -6.4±2.2% versus +1.3±3.6%). Courses of blood pressure, heart rate, and tympanic temperature were comparable for both treatments. Global and regional myocardial perfusion did not change significantly during either isolated ultrafiltration or isovolemic dialysis and did not differ between treatments. LV ejection fraction and wall motion score index did not change significantly during either treatment. Regional LV systolic dysfunction developed in 1 patient during isolated ultrafiltration and in 3 patients during isovolemic dialysis. In conclusion, global and regional myocardial perfusion were not compromised by 60 min of isolated ultrafiltration or isovolemic dialysis. Regional LV systolic dysfunction developed during isolated ultrafiltration and isovolemic dialysis, suggesting that, besides hypovolemia, dialysis-associated factors may be involved in the pathogenesis of hemodialysis-induced regional LV dysfunction

Supplemental Material, sj-docx-1-ptd-10.1177_08968608231198984 - Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways

Supplemental Material, sj-docx-1-ptd-10.1177_08968608231198984 for Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways by Bernardo Faria, Mariana Gaya da Costa, Anita H Meter-Arkema, Stefan P Berger, Carla Lima, Catia Pêgo, Jacob van den Born, Casper FM Franssen, Mohamed R Daha, Manuel Pestana, Marc A Seelen and Felix Poppelaars in Peritoneal Dialysis International</p