Glucose Exposure in Peritoneal Dialysis Is a Significant Factor Predicting Peritonitis

INTRODUCTION: Loss of residual renal function (RRF) as well as high peritoneal glucose exposure are associated with increased peritonitis frequency in peritoneal dialysis (PD) patients. Our objective was to investigate the contribution of RRF and peritoneal glucose exposure to peritonitis in PD patients. METHODS: In this prospective longitudinal cohort study, 105 incident end-stage renal disease patients that started PD between January 2006 and 2015 were studied. Follow-up was 5 years with censoring at death or switch to another treatment modality. Cox regression models were used to calculate the association between glucose exposure, RRF, and peritonitis. Kaplan-Meier analysis was used to examine the difference in occurrence of peritonitis between patients with high and low glucose exposure and between those with and without residual diuresis. RESULTS: One hundred and five patients were followed for a mean of 23 months. Fifty-one patients developed a peritonitis. Cox regression models at 6 months showed that glucose exposure and not residual diuresis significantly predicted PD peritonitis. Kaplan-Meier analysis after 6 months of follow-up showed that time to first PD peritonitis was significantly longer in the low glucose exposure group. Similarly, patients with RRF had a significantly longer interval to first peritonitis compared to patients without RRF. CONCLUSION: A higher exposure to glucose rather than loss of RRF is associated with an increased risk of peritonitis. This confirms the detrimental effects of glycemic harm to the peritoneal host defense on invading microorganisms and argues for the use of the lowest PD glucose concentrations possible

Increased Hepato-Splanchnic Vasoconstriction in Diabetics during Regular Hemodialysis

BACKGROUND AND OBJECTIVES:Ultrafiltration (UF) of excess fluid activates numerous compensatory mechanisms during hemodialysis (HD). The increase of both total peripheral and splanchnic vascular resistance is considered essential in maintaining hemodynamic stability. The aim of this study was to evaluate the extent of UF-induced changes in hepato-splanchnic blood flow and resistance in a group of maintenance HD patients during regular dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Hepato-splanchnic flow resistance index (RI) and hepato-splanchnic perfusion index (QI) were measured in 12 chronic HD patients using a modified, non-invasive Indocyaningreen (ICG) dilution method. During a midweek dialysis session we determined RI, QI, ICG disappearance rate (kICG), plasma volume (Vp), hematocrit (Hct), mean arterial blood pressure (MAP) and heart rate (HR) at four times in hourly intervals (t1 to t4). Dialysis settings were standardized and all patient studies were done in duplicate. RESULTS:In the whole study group mean UF volume was 1.86 ± 0.46 L, Vp dropped from 3.65 ± 0.77L at t1 to 3.40 ± 0.78L at t4, and all patients remained hemodynamically stable. In all patients RI significantly increased from 12.40 ± 4.21 mmHg∙s∙m2/mL at t1 to 14.94 ± 6.36 mmHg∙s∙m2/mL at t4 while QI significantly decreased from 0.61 ± 0.22 at t1 to 0.52 ± 0.20 L/min/m2 at t4, indicating active vasoconstriction. In diabetic subjects, however, RI was significantly larger than in non-diabetics at all time points. QI was lower in diabetic subjects. CONCLUSIONS:In chronic HD-patients hepato-splanchnic blood flow substantially decreases during moderate UF as a result of an active splanchnic vasoconstriction. Our data indicate that diabetic HD-patients are particularly prone to splanchnic ischemia and might therefore have an increased risk for bacterial translocation, endotoxemia and systemic inflammation

Investigation into cardiac sympathetic innervation during the commencement of haemodialysis in patients with chronic kidney disease

Background: Patients with chronic kidney disease (CKD) who undergo chronic haemodialysis (HD) show altered sympathetic tone, which is related to a higher cardiovascular mortality. The purpose of this study was to investigate the effect of transition from pre-HD to HD on cardiac sympathetic innervation. Methods: Eighteen patients aged 58 ± 18 years (mean ± standard deviation [SD]), 13 males and five females, with stage 5 CKD and nine healthy control subjects aged 52 ± 17 (mean ± SD), three males and six females, were included in this prospective study between May 2010 and December 2013. All patients underwent 123I-labelled meta-iodobenzylguanidine (123I-MIBG) scintigraphy for cardiac sympathetic innervation and electrocardiographically gated adenosine stress and rest 99mTc-labelled tetrofosmin single-photon emission computed tomography for myocardial perfusion imaging prior to (pre-HD) and 6 months after the start of HD. Results of 123I-MIBG scans in patients were compared to controls. Impaired cardiac sympathetic innervation was defined as late heart-to-mediastinum ratio (HMR) < 2.0. Results: Mean late HMR was lower in patients during HD (2.3) than in controls (2.9) (p = 0.035); however, in patients it did not differ between pre-HD and after the start of HD. During HD, two patients showed new sympathetic innervation abnormalities, and in three patients innervation abnormalities seemed to coincide with myocardial perfusion abnormalities. Conclusions: CKD patients show cardiac sympathetic innervation abnormalities, which do not seem to progress during the maintenance HD. The relationship between sympathetic innervation abnormalities and myocardial perfusion abnormalities in HD patients needs further exploration

Urinary 3-hydroxyisovaleryl carnitine excretion, protein energy malnutrition and risk of all-cause mortality in kidney transplant recipients:Results from the TransplantLines cohort studies

Background: Leucine is an essential amino acid and a potent stimulator of muscle protein synthesis. Since muscle wasting is a major risk factor for mortality in kidney transplant recipients (KTR), dietary leucine intake might be linked to long-term mortality. Urinary 3-hydroxyisovaleryl carnitine (3-HIC) excretion, a functional marker of marginal biotin deficiency, may also serve as a marker for dietary leucine intake. Objective: In this study we aimed to investigate the cross-sectional determinants of urinary 3-HIC excretion and to prospectively investigate the association of urinary 3-HIC excretion with all-cause mortality in KTR. Design: Urinary 3-HIC excretion and plasma biotin were measured in a longitudinal cohort of 694 stable KTR. Cross-sectional and prospective analyses were performed using ordinary least squares linear regression analyses and Cox regression analyses, respectively. Results: In KTR (57% male, 53 +/- 13 years, estimated glomerular filtration rate 45 +/- 19 mL/min/1.73 m(2)), urinary 3-HIC excretion (0.80 [0.57-1.16] mu mol/24 h) was significantly associated with plasma biotin (std. beta = -0.17; P 45%. During median follow-up for 5.4 [4.8-6.1] years, 150 (22%) patients died. Log(2)-transformed urinary 3-HIC excretion was inversely associated with all-cause mortality (HR: 0.52 [0.43-0.63]; P < 0.001). This association was independent of potential confounders. Conclusions: Urinary 3-HIC excretion more strongly serves as a marker of leucine intake than of biotin status. A higher urinary 3-HIC excretion is associated with a lower risk of all-cause mortality. Future studies are warranted to explore the underlying mechanism. (C) 2020 The Authors. Published by Elsevier Ltd

Pitfalls when comparing COVID-19-related outcomes across studies-lessons learnt from the ERACODA collaboration

Reported outcomes, such as incidence rates of mortality and intensive care unit admission, vary widely across epidemiological coronavirus disease 2019 (COVID-19) studies, including in the nephrology field. This variation can in part be explained by differences in patient characteristics, but also methodological aspects must be considered. In this review, we reflect on the methodological factors that contribute to the observed variation in COVID-19-related outcomes and their risk factors that are identified in the various studies. We focus on issues that arose during the design and analysis phase of the European Renal Association COVID-19 Database (ERACODA), and use examples from recently published reports on COVID-19 to illustrate these issues

Dilatation tracheoscopy for laryngeal and tracheal stenosis in patients with Wegener’s granulomatosis

Wegener’s granulomatosis (WG) frequently involves the subglottis and trachea and may compromise the upper airway. The objective of this study is to evaluate retrospectively the effect of treatment of subglottic stenosis (SGS) and tracheal stenosis (TS) by dilatation tracheoscopy (DT) in patients with WG. We performed a cohort study on all patients who underwent DT between February 2001 and September 2005 in our institution. From this cohort we identified a total of nine WG patients. In all patients, clinical, serological and histopathological data had been prospectively collected by a standardized protocol from the time point of diagnosis. In the nine patients that were identified with SGS or TS due to WG (eight women and one man), a total of 22 DT’s were performed. Two patients needed a tracheostoma (one temporarily). The mean follow-up after the first DT was 25.4 ± 14.1 months. Two patients did not experience a recurrence of SGS or TS. Six patients required a second DT without recurrence of local disease. The remaining patient underwent 8 DT's in a 4-year period. DT can offer a simple and repeatable solution to SGS and TS due to WG. Seven of the nine patients required more than one dilatation and some patients experience a functional restriction. One patient has a definitive tracheostoma

Plasma creatine concentration is associated with incident hypertension in a cohort enriched for the presence of high urinary albumin concentration:the Prevention of Renal and Vascular Endstage Disease study

: Hypertension is a major risk factor for cardiovascular disease, kidney disease, and premature death. Increased levels of creatine kinase are associated with development of hypertension. However, it is unknown if creatine, a substrate of CK, is associated with the development of hypertension. We therefore, aimed to investigate the association between plasma creatine concentration and incident hypertension. METHODS: We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the population-based PREVEND study. The study outcome was incident hypertension, defined as either a SBP of at least 140 mmHg, a DBP of at least 90 mmHg, or the new usage of antihypertensive drugs. Participants with hypertension at baseline were excluded. RESULTS: We included 3135 participants (46% men) aged 49 ± 10 years. Mean plasma creatine concentrations were 36.2 ± 17.5 μmol/l, with higher concentrations in women than in men (42.2 ± 17.6 versus 29.2 ± 17.6 μmol/l; P < 0.001). During a median of 7.1 [interquartile range: 3.6–7.6] years of follow-up, 927 participants developed incident hypertension. Higher plasma creatine concentrations were associated with an increased risk of incident hypertension [HR per doubling of plasma creatine: 1.21 (95% confidence interval: 1.10–1.34); P < 0.001], which remained significant after adjustment for potential confounders. Sex-stratified analyses demonstrated higher plasma creatine that was independently associated with an increased risk of incident hypertension in men [hazard ratio: 1.26 (95% CI 1.11–1.44); P < 0.001], but not in women (hazard ratio: 1.13 (95% CI 0.96–1.33); P = 0.14]. Causal pathway analyses demonstrate that the association was not explained by sodium or protein intake. CONCLUSION: Higher plasma creatine is associated with an increased risk of hypertension in men. Future studies are warranted to determine the underlying mechanisms

Dietary lithium intake, graft failure and mortality in kidney transplant recipients

BACKGROUND &amp; AIMS: Long-term high dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation, or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival.METHODS: Urinary lithium concentration was measured using inductively coupled plasma-mass-spectrometry in 642 stable kidney transplant recipients. Graft failure was defined as start of dialysis or re-transplantation, and kidney function decline was defined as doubling of serum creatinine.RESULTS: Median [interquartile range] urinary lithium excretion was 3.03 [2.31-4.01] μmol/24 h. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 [4.5-6.0] years, 79 (12%) KTR developed graft failure and 127 (20%) KTR developed kidney function decline. Higher urinary lithium excretion was associated with lower risk of graft failure (hazard ratio [95% confidence interval]: 0.54 [0.38-0.79] per log2 μmol/24 h) and kidney function decline (HR [95% CI]: 0.73 [0.54-0.99] per log2 μmol/24 h). These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was significant effect modification by use of proliferation inhibitors (P = 0.05) and baseline eGFR (P &lt; 0.001), with higher urinary lithium excretion being more protective in KTR not using proliferation inhibitors and in KTR with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with reduced risk of all-cause mortality (HR [95% CI]: 0.64 [0.49-0.83]; P = 0.001).CONCLUSION: Dietary lithium intake may be a potentially modifiable-yet rather overlooked-risk factor for adverse long-term kidney graft outcomes and patient survival.</p