Peritoneal dialysis (PD)-associated peritonitis is a serious complication of PD and prevention and treatment of such is important in reducing patient morbidity and mortality. The ISPD 2022 updated ...recommendations have revised and clarified definitions for refractory peritonitis, relapsing peritonitis, peritonitis-associated catheter removal, PD-associated haemodialysis transfer, peritonitis-associated death and peritonitis-associated hospitalisation. New peritonitis categories and outcomes including pre-PD peritonitis, enteric peritonitis, catheter-related peritonitis and medical cure are defined. The new targets recommended for overall peritonitis rate should be no more than 0.40 episodes per year at risk and the percentage of patients free of peritonitis per unit time should be targeted at >80% per year. Revised recommendations regarding management of contamination of PD systems, antibiotic prophylaxis for invasive procedures and PD training and reassessment are included. New recommendations regarding management of modifiable peritonitis risk factors like domestic pets, hypokalaemia and histamine-2 receptor antagonists are highlighted. Updated recommendations regarding empirical antibiotic selection and dosage of antibiotics and also treatment of peritonitis due to specific microorganisms are made with new recommendation regarding adjunctive oral N-acetylcysteine therapy for mitigating aminoglycoside ototoxicity. Areas for future research in prevention and treatment of PD-related peritonitis are suggested.
Graphical Abstract
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Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there ...has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled “Early Identification and Intervention in CKD.” Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.
Current hemodialysis techniques fail to efficiently remove the protein-bound uremic toxins p-cresyl sulfate and indoxyl sulfate due to their high degree of albumin binding. Ibuprofen, which shares ...the same primary albumin binding site with p-cresyl sulfate and indoxyl sulfate, can be infused during hemodialysis to displace these toxins, thereby augmenting their removal.
We infused 800 mg ibuprofen into the arterial bloodline between minutes 21 and 40 of a conventional 4-hour high-flux hemodialysis treatment. We measured arterial, venous, and dialysate outlet concentrations of indoxyl sulfate, p-cresyl sulfate, tryptophan, ibuprofen, urea, and creatinine before, during, and after the ibuprofen infusion. We report clearances of p-cresyl sulfate and indoxyl sulfate before and during ibuprofen infusion and dialysate concentrations of protein-bound uremic toxins normalized to each patient's average preinfusion concentrations.
We studied 18 patients on maintenance hemodialysis: age 36±11 years old, ten women, and mean vintage of 37±37 months. Compared with during the preinfusion period, the median (interquartile range) clearances of indoxyl sulfate and p-cresyl sulfate increased during ibuprofen infusion from 6.0 (6.5) to 20.2 (27.1) ml/min and from 4.4 (6.7) to 14.9 (27.1) ml/min (each
<0.001), respectively. Relative median (interquartile range) protein-bound uremic toxin dialysate outlet levels increased from preinfusion 1.0 (reference) to 2.4 (1.2) for indoxyl sulfate and to 2.4 (1.0) for p-cresyl sulfate (each
<0.001). Although median serum post- and predialyzer levels in the preinfusion period were similar, infusion led to a marked drop in serum postdialyzer levels for both indoxyl sulfate and p-cresyl sulfate (-1.0 and -0.3 mg/dl, respectively; each
<0.001). The removal of the nonprotein-bound solutes creatinine and urea was not increased by the ibuprofen infusion.
Infusion of ibuprofen into the arterial bloodline during hemodialysis significantly increases the dialytic removal of indoxyl sulfate and p-cresyl sulfate and thereby, leads to greater reduction in their serum levels.
Climate change has led to significant rise of 0.8°C-0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves ...(extreme heat events). Climate change has also been increasingly connected to detrimental human health. One of the consequences of climate-related extreme heat exposure is dehydration and volume loss, leading to acute mortality from exacerbations of pre-existing chronic disease, as well as from outright heat exhaustion and heat stroke. Recent studies have also shown that recurrent heat exposure with physical exertion and inadequate hydration can lead to CKD that is distinct from that caused by diabetes, hypertension, or GN. Epidemics of CKD consistent with heat stress nephropathy are now occurring across the world. Here, we describe this disease, discuss the locations where it appears to be manifesting, link it with increasing temperatures, and discuss ongoing attempts to prevent the disease. Heat stress nephropathy may represent one of the first epidemics due to global warming. Government, industry, and health policy makers in the impacted regions should place greater emphasis on occupational and community interventions.
Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. ...Some treatments have been assessed in randomized trials, but most such trials have been too small to detect treatment effects of a magnitude that would be realistic to achieve with a single intervention. Therefore, KDIGO convened an international, multidisciplinary controversies conference titled “Challenges in the Conduct of Clinical Trials in Nephrology” to identify the key barriers to conducting trials in patients with kidney disease. The conference began with plenary talks focusing on the key areas of discussion that included appropriate trial design (covering identification and evaluation of kidney and nonkidney disease outcomes) and sensible trial execution (with particular emphasis on streamlining both design and conduct). Break out group discussions followed in which the key areas of agreement and remaining controversy were identified. Here we summarize the main findings from the conference and set out a range of potential solutions. If followed, these solutions could ensure future trials among people with kidney disease are sufficiently robust to provide reliable answers and are not constrained by inappropriate complexities in design or conduct.
Originally developed for use in type 2 diabetes mellitus (T2DM), sodium–glucose co-transporter-2 (SGLT2) inhibitors demonstrated diverse cardiovascular- and kidney-protective effects in large outcome ...trials. Their subsequent approval as a treatment for chronic kidney disease (CKD) marked a pivotal shift in the landscape of CKD management. Further to this, the approval of dapagliflozin and empagliflozin for use in patients with CKD with and without T2DM afforded new treatment opportunities for this population. SGLT2 inhibitors provide an effective treatment for CKD with a favorable safety profile. However, their uptake has been slow, especially among patients without T2DM, owing perhaps to a lack of certainty and familiarity among health care professionals. As the landscape of CKD management continues to evolve, health care professionals should remain knowledgeable about these changes, and implement new guideline recommendations promptly to avoid therapeutic inertia. SGLT2 inhibitors are recommended for patients with CKD with or without T2DM and are foundational agents to support cardiovascular, kidney, and metabolic health. In this review, we provide evidence-based answers to questions that may be asked in the clinic regarding the use of SGLT2 inhibitors to treat CKD.
Uric Acid and Long-term Outcomes in CKD Madero, Magdalena, MD; Sarnak, Mark J., MD; Wang, Xuelei, MS ...
American journal of kidney diseases,
05/2009, Letnik:
53, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background Hyperuricemia is prevalent in patients with chronic kidney disease (CKD); however, data are limited about the relationship of uric acid levels with long-term outcomes in this patient ...population. Study Design Cohort study. Setting & Participants The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N = 840) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This analysis included 838 patients. Predictor Uric acid level. Outcomes & Measurements The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular disease (CVD) mortality, and kidney failure. Results Mean age was 52 ± 12 (SD) years, glomerular filtration rate was 33 ± 12 mL/min/1.73 m2 , and uric acid level was 7.63 ± 1.66 mg/dL. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) died of CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause mortality (hazard ratio HR, 1.57; 95% confidence interval CI, 1.07 to 2.32), a trend toward CVD mortality (HR, 1.47; 95% CI, 0.90 to 2.39), and no association with kidney failure (HR, 1.20; 95% CI, 0.95 to 1.51) compared with the lowest tertile. In continuous analyses, a 1-mg/dL greater uric acid level was associated with 17% increased risk of all-cause mortality (HR, 1.17; 95% CI, 1.05 to 1.30) and 16% increased risk of CVD mortality (HR, 1.16; 95% CI, 1.01 to 1.33), but was not associated with kidney failure (HR, 1.02; 95% CI, 0.97 to 1.07). Limitations Primary analyses were based on a single measurement of uric acid. Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD. Conclusions In patients with stages 3 to 4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality, but not kidney failure.
Chronic kidney disease (CKD) is a worldwide public health problem, and proteinuria may accelerate the progression of CKD, being oxidative stress a common mechanism in nondiabetic or diabetic ...proteinuric kidney disease. This study was designed to evaluate the effect of the dietary supplementation with curcumin (CUR) on the redox status and the nuclear factor erythroid 2-related factor 2 (Nrf2) activation in patients with nondiabetic or diabetic proteinuric CKD.
Randomized double-blind placebo-controlled clinical trial.
A total of 101 Mexican patients from the National Institute of Cardiology "Ignacio Chavez", with nondiabetic or diabetic proteinuric CKD (proteinuria ≥ 1 g protein/24 hours), aged 20 to 70 years; 60% were male, and 51% were diabetic.
Patients with nondiabetic proteinuric CKD received placebo (n = 26) or CUR 320 mg/day (n = 24) for 8 weeks, and patients with diabetic proteinuric CKD were intervened with placebo (n = 23) or CUR 320 mg/day (n = 28) for the same period.
Anthropometrical, clinical, and biochemical characteristics, as well as oxidative stress markers, antioxidant enzyme activities and Nrf2 activation were evaluated at baseline and after intervention.
The intervention with CUR did not improve proteinuria, estimated glomerular filtration rate, or lipid profile. However, in plasma, CUR attenuated lipid peroxidation in individuals with nondiabetic proteinuric CKD (P<.05) and enhanced the antioxidant capacity in subjects with diabetic proteinuric CKD (P<.05). No effect of CUR was observed on the antioxidant enzymes activities or Nrf2 activation.
Dietary supplementation with CUR has the potential to reduce oxidative stress in Mexican patients with nondiabetic or diabetic proteinuric CKD. Studies with higher doses of CUR and longer follow-up are granted to confirm our findings.
An epidemic of chronic kidney disease (CKD) has been observed in Central America among workers in the sugarcane fields. One hypothesis is that the CKD may be caused by recurrent heat stress and ...dehydration, and potentially by hyperuricemia. Accordingly, we developed a murine model of kidney injury associated with recurrent heat stress. In the current experiment, we tested whether treatment with allopurinol (a xanthine oxidase inhibitor that reduces serum urate) provides renal protection against recurrent heat stress and dehydration. Eight-week-old male C57BL/6 mice were subjected to recurrent heat stress (39.5°C for 30 min, 7 times daily, for 5 wk) with or without allopurinol treatment and were compared with control animals with or without allopurinol treatment. Mice were allowed ad libitum access to normal laboratory chow (Harlan Teklad). Kidney histology, liver histology, and renal function were examined. Heat stress conferred both kidney and liver injury. Kidneys showed loss of proximal tubules, infiltration of monocyte/macrophages, and interstitial collagen deposition, while livers of heat-stressed mice displayed an increase in macrophages, collagen deposition, and myofibroblasts. Allopurinol provided significant protection and improved renal function in the heat-stressed mice. The renal protection was associated with reduction in intrarenal uric acid concentration and heat shock protein 70 expression. Heat stress-induced renal and liver injury can be protected with allopurinol treatment. We recommend a clinical trial of allopurinol for individuals developing renal injury in rural areas of Central America where the epidemic of chronic kidney disease is occurring.
We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the ...long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.
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