Systemic and intraperitoneal interleukin‐6 system during the first year of peritoneal dialysis

Perit Dial Int. 2006 Jan-Feb;26(1):53-63. Systemic and intraperitoneal interleukin-6 system during the first year of peritoneal dialysis. Pecoits-Filho R, Carvalho MJ, Stenvinkel P, Lindholm B, Heimbürger O. Division of Renal Medicine and Baxter Novum, Karolinska Institutet, K-56, Huddinge University Hospital, 141 86 Stockholm, Sweden. [email protected] Comment in: Perit Dial Int. 2006 Jan-Feb;26(1):35-7. Abstract OBJECTIVE: To investigate if intraperitoneal and systemic interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) are related to each other and to peritoneal solute transport rate (PSTR). DESIGN: Longitudinal study in retrospectively selected patients. SETTING: Peritoneal dialysis (PD) unit of a university-based hospital. PATIENTS AND METHODS: 31 PD patients on treatment with conventional glucose-based solutions participated in a longitudinal study. IL-6 and sIL-6R were measured in plasma and overnight effluent, both at baseline and after 12 +/- 2 months on PD. C-reactive protein (CRP) and serum albumin were used as surrogate markers of inflammation. PSTR of small solutes was evaluated using the dialysate-to-plasma ratio (D/P) of creatinine after a 4-hour dwell; PSTR of large solutes was evaluated using the 24-hour D/P ratio of albumin. RESULTS: D/P creat increased over time (0.67 +/- 0.15 vs 0.80 +/- 0.11, p or = median had higher (p or = median [24.7 (16.5 - 38.5) pg/mL] compared to patients with IL-6 < median [14.1 (10 - 25.7) pg/mL]. Neither CRP nor albumin changed over time on PD, although they were closely linked to plasma IL-6 levels. A strong positive correlation was found between D/P creat and dialysate IL-6 (rho = 0.77, p < 0.0001) at baseline, but not at 1 year. In contrast, there was a significant correlation between D/P creat and dialysate sIL-6R (rho = 0.39, p < 0.05) at 1 year, but not at baseline. At 1 year, 17 patients with increasing PSTR had higher increases in dialysate IL-6 (28 +/- 26 vs -21 +/- 78 pg/mL, p < 0.05) and levels of dialysate sIL-6R (693 +/- 392 vs 394 +/- 274 pg/mL, p = 0.05) compared to patients with stable PSTR (n = 11). Patients who had peritonitis presented higher baseline serum IL-6 concentration (6.8 +/- 1.0 pg/mL) compared with patients without peritonitis (4.0 +/- 0.6 pg/mL, p < 0.05). Finally, both at baseline and after 1 year, there were significant correlations between plasma and dialysate IL-6 (rho = 0.46, p < 0.05, and rho = 0.40, p < 0.05) respectively. CONCLUSIONS: These findings indicate that, (1) intraperitoneal and systemic inflammation increase in PD patients during the first year of therapy; (2) intraperitoneal and systemic inflammation may be interrelated and the IL-6 system may be the link; (3) the IL-6 system (both intraperitoneal and systemic) is associated with PSTR, particularly in the early phase of PD treatment, in which small and large solute transport are linked. Signs of a transition between acute and chronic inflammation were observed in the follow-up evaluation. Inflammation may, at least in part, be responsible for the development of a high PSTR, and this could be one reason for the high mortality in patients with high PSTR. PMID: 16538876 [PubMed - indexed for MEDLIN

Identifying critically important vascular access outcomes for trials in haemodialysis : an international survey with patients, caregivers and health professionals

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD

Blood pressure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

In September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis

Diagnostic performance of salivary urea nitrogen dipstick to detect and monitor acute kidney disease in patients with malaria

BACKGROUND: Acute kidney injury (AKI) is a common complication of malaria. In low resource settings, a lack of diagnostic tools and delayed treatment of malaria associated AKI lead to significant morbidity and mortality. The aim of this study was to assess the diagnostic performance of salivary urea nitrogen (SUN) dipstick to detect and monitor kidney disease [KD = AKI or acute kidney disease (AKD) without AKI] in malaria patients in Angola. METHODS: Patients 11–50 years old admitted with malaria at the Josina Machel (Maria-Pia) Hospital, Luanda, Angola, between 2nd March and 10th May 2016 were enrolled in this study. All participants had serum creatinine (sCr), blood urea nitrogen (BUN) and SUN dipstick tested at the time of recruitment and daily for up to 4 days. AKD without AKI refers to acute renal impairment which do not fulfilled the main criteria for AKI (increases in the baseline serum creatinine and/or decreases in urine output) according defined by the kidney disease improving global outcomes (KDIGO) guideline. RESULTS: Eight-six patients were admitted with malaria diagnosis (mean age 21.5 ± 9.4 years, 71% male) and 27 (32%) were diagnosed with KD. The mean (± SD) sCr and BUN of the KD group at admission (day 0) were 5.38 (± 5.42) and 99.4 (± 61.9) mg/dL, respectively. Three (3.5%) patients underwent haemodialysis and eight (9.3%) died within the first 4 days of hospital admission [5 (62.5%) with KD; 3 (37.5%) without kidney disease; p = 0.047]. The SUN threshold for KD diagnosis was tested pad #5 (SUN > 54 mg/dL). At this threshold, the SUN dipstick had a sensitivity of 67% and specificity of 98% to diagnose KD. The area under the receiver operating characteristics curve (ROC) for KD diagnosis on admission was 0.88 (95% CI 0.79–0.96). The SUN dipstick was most accurate at higher levels of BUN. CONCLUSION: The SUN dipstick had reasonable sensitivity and excellent specificity when used to diagnose KD in a cohort of patients with malaria in a resource-limited setting. Given the severity of presenting illness and kidney injury, the SUN dipstick diagnostic threshold was high (test pad #5). SUN may be used to detect AKI in patients with malaria in low resources settings, thus facilitating earlier access to adequate treatment, which may improve survival

A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy

Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10mg or placebo, as adjunct to standard care. The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m2; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were −3.5 and −4.7 mL/min/1.73m2/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin, and no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas

Diagnostic Performance of a Saliva Urea Nitrogen Dipstick to Detect Kidney Disease in Malawi

Introduction: Kidney disease (KD), including acute kidney injury, is common, severe and leads to significant mortality in the developing world. However, simple tools to facilitate diagnosis and guide treatment are lacking. We studied the diagnostic performance of saliva urea nitrogen (SUN) measured by dipstick to diagnose KD in a low-resource setting. Methods: Medical admissions to a tertiary hospital in Malawi had serum creatinine tested at presentation; SUN was measured using a dipstick. Patients with serum creatinine above normal range underwent serial measurements of SUN and blood urea nitrogen for up to 7 days. Hospital outcome was recorded in all patients. Results: A total of 742 patients were included (age 41 ± 17·3 years, 56.1% male); 146 (19.7%) had KD, including 114 (15.4%) with acute kidney injury. SUN >14 mg/dl had a sensitivity of 0.72 and a specificity of 0.87 to diagnose KD; specificity increased to 0.97 when SUN levels were combined with self-reported urine output. The diagnostic performance of SUN was comparable with the one of blood urea nitrogen (SUN area under curve, 0.82; 95% confidence interval, 0.78–0.87; blood urea nitrogen area under curve, 0.82; 95% confidence interval, 0.59–1.0). SUN >14 mg/dl on admission was an independent predictor of all-cause mortality (hazard ratio = 2.43 [95% confidence interval, 1.63–3.62]). Discussion: SUN measured by dipstick can be used to identify patients with KD in a low-resource setting. SUN is an independent predictor of mortality in this population

A Salivary Urea Nitrogen Dipstick to Detect Obstetric-Related Acute Kidney Disease in Malawi

Introduction: Obstetric-related acute kidney injury (AKI) is associated with adverse outcomes for mother and fetus, particularly in low-income countries. However, laboratory-independent tools to facilitate diagnosis are lacking. We assessed the diagnostic performance of a salivary urea nitrogen (SUN) dipstick to detect obstetric-related acute kidney disease in Malawi. / Methods: Women at high risk for AKI admitted to an obstetric unit in Blantyre, Malawi, were recruited between 21 September and 11 December 2015. Patients underwent serum creatinine (SCr) testing alongside measurement of SUN using a dipstick on admission, and every 48 hours thereafter if evidence of kidney disease was found. / Results: A total of 301 patients were included (mean age 25.9 years, 11% HIV positive). Of the patients, 23 (7.6%) had AKI, stage 1 in 47.8%, most commonly due to preeclampsia/eclampsia. Mean presenting SCr values were 108.8 ± 21.8 μmol/l (1.23 ± 0.25 mg/dl), 118 ± 34.45 μmol/l (1.33 ± 0.39 mg/dl), and 136.1 ± 30.4 μmol/l (1.54 ± 0.34 mg/dl) in AKI stages 1 to 3 respectively. SUN > 14 mg/dl had a sensitivity of 12.82% and a specificity of 97.33% to detect acute kidney disease; the area under the receiver operating characteristic curve was 0.551. In patients with normal SUN on admission, perinatal mortality was 11.8%, and was 25.0% if SUN was?> 14 mg/dl (P = 0.18). / Conclusion: The SUN dipstick was specific but insensitive when used to diagnose obstetric-related AKI. Limited biochemical derangement and low salivary urea concentrations due to physiological changes in pregnancy, as opposed to a technical limitation of the dipstick itself, are the likely reason for the lack of sensitivity in this study