The case for cautious consumption: NSAIDs in chronic kidney disease.

PURPOSE OF REVIEW: Strong epidemiological and pathologic evidence associates NSAIDs with kidney disease, both acute and chronic. Hence, the usage of NSAIDs has decreased in patients with, or at risk for, chronic kidney disease (CKD). Coupled with this has been a rise in use of opioids and other non-NSAID alternatives, which do come with significant, and underrecognized, risk of nonrenal adverse events. We review the literature to understand if this shift is appropriate or deleterious. RECENT FINDINGS: NSAIDs do have a low but tangible risk in causing acute kidney injury, electrolyte imbalances, and increasing blood pressure. However, their role in causing progressive kidney disease is due to long-term usage in high cumulative dosages, and the use of NSAIDs in combination with other agents. Alternatives such as opioids, tramadol, gabapentin and baclofen have weak evidence to support their use and strong evidence to show their harm in patients with CKD. SUMMARY: Tradeoffs are inherent in using active pharmaceuticals, and NSAIDs are no exception. Balancing potential benefits with possible adverse effects around pain management should be a part of every conversation for patients with kidney disease.

Potassium and Hypertension: A State-of-the-Art Review.

Hypertension is the single most important and modifiable risk factor for cardiovascular morbidity and mortality worldwide. Non pharmacologic interventions, in particular dietary modifications have been established to decrease blood pressure (BP) and hypertension related adverse cardiovascular events. Among those dietary modifications, sodium intake restriction dominates guidelines from professional organizations and has garnered the greatest attention from the mainstream media. Despite guidelines and media exhortations, dietary sodium intake globally has not noticeably changed over recent decades. Meanwhile, increasing dietary potassium intake has remained on the sidelines, despite similar BP-lowering effects. New research reveals a potential mechanism of action, with the elucidation of its effect on natriuresis via the potassium switch effect. Additionally, potassium-substituted salt has been shown to not only reduce BP, but also reduce the risk for stroke and cardiovascular mortality. With these data, we argue that the focus on dietary modification should shift from a sodium-focused to a sodium- and potassium-focused approach with an emphasis on intervention strategies which can easily be implemented into clinical practice.

Sodium-glucose Co-transporter-2 Inhibitors Causing Candida tropicalis Fungemia and Renal Abscess.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively newer class of medications, approved by the U.S. Food and Drug Administration in 2013 to treat type 2 diabetes mellitus. Over the past few years, the indications for SGLT2i have been expanded to decrease the risk of kidney disease and cardiovascular disease. SGLT2i are associated with an increased risk of euglycemic diabetic ketoacidosis, urinary tract infections, and genital mycotic infections. There are a few case reports of severe invasive fungal infections due to Candida in patients using SGLT2i. We present the case of Candida tropicalis fungemia and renal abscess in a patient on an SGLT2i.

Social determinants of health and dialysis modality selection in patients with advanced chronic kidney disease: A retrospective cohort study.

BACKGROUND: Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood. METHODS: Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation. RESULTS: The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m2, respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34-0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27-0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39-0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39-0.78)). CONCLUSIONS: Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these 'upstream' social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure.

High-Anion-Gap Metabolic Acidosis During a Prolonged Hospitalization Following Perforated Diverticulitis: An Educational Case Report.

Rationale: The metabolic acidoses are generally separated into 2 categories on the basis of an anion gap calculation: high-anion-gap and normal anion-gap metabolic acidosis. When a high-anion-gap metabolic acidosis (HAGMA) is not clearly explained by common etiologies and routine confirmatory testing, specialized testing can definitively establish rare diagnoses such as 5-oxoproline, d-lactate accumulation, or diethylene glycol toxicity. Presenting Concerns of the Patient: A 56-year-old woman had a prolonged hospital admission following perforated diverticulitis requiring sigmoid resection. Her hospitalization was complicated by feculent peritonitis and surgical wound dehiscence needing prolonged broad-spectrum antibiotics and wound debridements. She developed acute kidney injury and HAGMA in the hospital. Diagnoses: Chart review showed that she received a large cumulative dose of acetaminophen during her hospital stay. Laboratory studies showed markedly increased serum 5-oxoproline causing HAGMA. Interventions Including Prevention and Lifestyle: Patient was admitted to the intensive care unit and treated with N-acetylcysteine and renal replacement therapy. Outcomes: After admission to the intensive care unit, the patient continued to require vasopressor and ventilatory support for septic shock and a ventilator-associated pneumonia. After an initial recovery and resolution of her HAGMA, she subsequently suffered recurrent aspirations which were fatal. Teaching points: 1. The acronym GOLD MARK is useful when assessing patients with HAGMA and most causes of HAGMA can be established with routine testing.2. When the etiology of HAGMA remains unclear, additional testing can be required to diagnose rare causes of HAGMA.3. Rare causes of HAGMA are diethylene glycol, 5-oxoproline, and d-lactate accumulation.4. Acidosis secondary to 5-oxoproline accumulation can occur even with "therapeutic" doses of acetaminophen in patients receiving it regularly for a prolonged period and who have depleted glutathione stores.5. Risk factors for glutathione depletion include malnutrition, older age, sepsis, pregnancy, multiple chronic illnesses, and chronic kidney disease.

Justification: Les acidoses métaboliques sont généralement classées en deux catégories sur la base d'un calcul de trou anionique : les acidoses métaboliques à trou anionique élevé (HAGMA ­ High anion gap metabolic acidosis) et les acidoses métaboliques à trou anionique normal. Lorsque l'acidose métabolique à trou anionique élevé n'est pas clairement expliquée par des étiologies courantes et des tests de confirmation de routine, des tests spécialisés peuvent établir de façon définitive des diagnostics rares tels que l'accumulation de 5-oxoproline, l'accumulation de D-lactate ou une toxicité du diéthylène glycol. Présentation du cas: Une femme de 56 ans hospitalisée de façon prolongée à la suite d'une diverticulite perforée nécessitant une résection du sigmoïde. L'hospitalisation a été compliquée par une péritonite purulente et une déhiscence de la plaie chirurgicale ayant nécessité un débridement de la plaie et une antibiothérapie à large spectre prolongée. La patiente a développé une insuffisance rénale aiguë (IRA) et une HAGMA durant son séjour à l'hôpital. Diagnostic: L'examen du dossier a montré que la patiente avait reçu une dose cumulative importante d'acétaminophène pendant son séjour à l'hôpital. Des analyses en laboratoire ont montré une augmentation marquée de la 5-oxoproline sérique ayant causé l'HAGMA. Interventions y compris prévention et mode de vie: La patiente a été admise à l'unité des soins intensifs et traitée par N-acétylcystéine et thérapie de remplacement rénal (TRR). Résultats: Après son admission à l'USI, la patiente a continué d'avoir besoin de vasopresseur et d'assistance respiratoire en raison d'un choc septique et d'une pneumonie associée au ventilateur. Après un rétablissement initial et la résolution de son HAGMA, la patiente a ensuite dû subir des aspirations récurrentes qui lui ont été fatales. Enseignements tirés: 1. L'acronyme GOLD MARK est utile lors de l'évaluation des patients atteints d'HAGMA; la plupart des causes d'HAGMA peuvent être établies avec des tests de routine.2. Lorsque l'étiologie de l'HAGMA reste incertaine, des tests supplémentaires peuvent être nécessaires pour diagnostiquer les causes rares de l'HAGMA.3. Les causes rares de HAGMA sont une accumulation de diéthylène glycol, de 5-oxoproline et de D-lactate.4. L'acidose secondaire à une accumulation de 5-oxoproline peut se produire même avec des doses « thérapeutiques ¼ d'acétaminophène chez les patients qui l'ont reçu régulièrement pendant une période prolongée et qui ont épuisé leurs réserves de glutathion.5. Les facteurs de risque pour l'épuisement des réserves de glutathion incluent la malnutrition, l'âge plus avancé, la septicémie, la grossesse, les maladies chroniques multiples et l'insuffisance rénale chronique.

Initial and Recurrent Hyperkalemia Events in Patients With CKD in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The risk of hyperkalemia is elevated in chronic kidney disease (CKD); however, the initial and recurrent risk among older individuals is less clear. OBJECTIVES: We set out to examine the initial and 1-year recurrent risk of hyperkalemia by level of kidney function (estimated glomerular filtration rate, eGFR) in older adults (≥66 years old). DESIGN: Population-based, retrospective cohort study. SETTINGS: Ontario, Canada. PARTICIPANTS: 905 167 individuals (≥66 years old) from 2008 to 2015. MEASUREMENTS: Serum potassium values. METHODS: Individuals were stratified by eGFR (≥90, 60-89, 30-59, 15-29 mL/min/1.73 m2) and examined for the risk of incident hyperkalemia (K ≥ 5.5 mEq/L) using adjusted Cox proportional hazards models. The 1-year risk of recurrent hyperkalemia was examined using multivariable Andersen-Gill models. RESULTS: Among a population of 905 167 individuals (15% eGFR ≥ 90, 58% eGFR 60-89, 25% eGFR 30-59, 3% eGFR 15-29) with a potassium measurement, there were a total of 18 979 (2.1%) individuals with hyperkalemia identified. The event rate (per 1000 person-years) and adjusted hazard ratio (HR) of hyperkalemia was inversely associated with eGFR (mL/min; eGFR >90 mL/min: 8.8, referent, 60-89 mL/min: 11.8 HR 1.41; eGFR 30-59: 39.8, HR 4.37; eGFR 15-29: 133.6, 13.65) and with an increasing urine albumin-to-creatinine ratio (ACR, mg/mmol; ACR< 3: 14, referent, ACR 3-30: 35.1, HR 1.98; ACR >30: 93.7, 4.71). The 1-year event rate and adjusted risk of recurrent hyperkalemia was similarly inversely associated with eGFR (eGFR ≥ 90: 10.1, referent, eGFR 60-89: 14.4, HR 1.47; eGFR 30-59: 54.8, HR 4.90; eGFR 15-29: 208.0, HR 12.98). Among individuals with a baseline eGFR of 30 to 59 and 15 to 29, 0.9 and 3.8% had greater than 2 hyperkalemia events. The relative risk of initial and recurrent hyperkalemia was marginally higher with RAAS blockade. Roughly 1 in 4 individuals with hyperkalemia required hospitalization the day of or within 30 days after their hyperkalemia event. LIMITATIONS: Limited to individuals aged 66 years and above. CONCLUSIONS: Patients with low eGFR are at a high risk of initial and recurrent hyperkalemia. TRIAL REGISTRATION: N/A.

CONTEXTE: Le risque d'hyperkaliémie est élevé en contexte d'insuffisance rénale chronique (IRC). On en sait cependant peu sur le risque initial et récurrent d'hyperkaliémie chez les patients âgés. OBJECTIF: Nous avons examiné le risque initial d'hyperkaliémie et le risque de récurrence sur une année selon le niveau de fonction rénale (débit de filtration glomérulaire estimé [DFGe]) chez les patients âgés (plus de 66 ans). TYPE D'ÉTUDE: Étude de cohorte rétrospective basée sur une population. CADRE: Ontario, Canada. SUJETS: L'étude porte sur un total de 905 167 individus (âgés de 66 ans et plus) entre 2008 et 2015. MESURES: Les valeurs de potassium sérique. MÉTHODOLOGIE: Les individus ont été stratifiés en fonction du DFGe (≥90, 60-89, 30-59, 15-29 ml/min/1.73m2) et examinés pour le risque d'hyperkaliémie incidente (K ≥ 5,5 mEq/L) à l'aide de modèles de risques proportionnels de Cox corrigés. Le risque de récurrence sur un an a été examiné avec des modèles multivariés d'Andersen-Gill. RÉSULTATS: Parmi les 905 167 individus disposant d'une mesure de potassium sérique (15 % avec un DFGe ≥ 90; 58 % avec un DFGe de 60-89; 25 % avec un DFGe de 30-59; et 3 % avec un DFGe de 15-29), on a recensé 18 979 individus (2,1 %) présentant une hyperkaliémie. Le taux d'événements (pour 1 000 années-personnes) et le rapport de risque corrigé (RR) de l'hyperkaliémie étaient inversement associés au DFGe (ml/min). Ainsi, un DFGe > 90 ml/min a été associé à 8,8 événements pour 1 000 années-personnes (EV) et constituait le référent pour le RR; ces valeurs pour les autres niveaux de DFGe étaient les suivantes: 11,8 EV (RR = 1,41) pour un DFGe 60-89; 39,8 EV (RR = 4,37) pour un DFGe de 30-59; et 133,6 EV (RR = 13,65) pour un DFGe de 15-29. L'accroissement de ces valeurs a également été associé à un accroissement du rapport albumine/créatinine dans l'urine (RAC mg/mmol). Ainsi, un RAC < 3 a été associé à 14 EV et constituait le référent pour le RR, tandis que 35,1 EV (RR = 1,98) ont été observés pour un RAC de 3-30; et que ce nombre passait à 93,7 EV (RR=4,71) pour un RAC > 30. Le taux d'événements sur un an et le risque corrigé d'hyperkaliémie récidivante étaient eux aussi inversement associés au DFGe: 10,1 EV (RR = valeur de référence) pour un DFGe ≥ 90; 14,4 EV (RR=1,47) pour un DFGe 60-89; 54,8 EV (RR=4,90) pour un DFGe 30-59; et 208,0 EV (RR=12,98) pour un DFGe 15-29. Parmi les individus présentant un DFGe initial de 30-59 et de 15-29 ml/min/1,73m2, un certain nombre de patients avaient vécu plus de deux événements d'hyperkaliémie (respectivement 0,9 % et 3,8 %). Le risque relatif d'hyperkaliémie initiale et récurrente était légèrement plus élevé avec le blocage du SRAA. Environ une personne sur quatre atteinte d'hyperkaliémie a dû être hospitalisée le jour de l'événement ou dans les 30 jours suivant celui-ci. LIMITES: L'étude a été limitée aux personnes âgées de 66 ans et plus. CONCLUSION: Les patients présentant un faible taux de DFGe présentent un risque élevé d'hyperkaliémie initiale et récurrente.

Unintended Consequences: Perils of Renal Revascularization for Severe Hypertension.

Revascularization of atherosclerotic renal artery stenosis may cure hypertension, but paradoxically, improvement in systemic blood pressure in response to successful revascularization may precipitate ischemia in other organs affected by previously silent atherosclerotic disease. We describe bowel ischemia secondary to preexisting celiac artery stenosis after revascularisation. Prior knowledge of multivessel disease facilitated prompt diagnosis and management of this condition.

Retrospective study of patients on hybrid dialysis: Single-center data from North America.

Hybrid dialysis involves combining peritoneal and hemodialysis (HD) in patients with end-stage renal disease. Its reported use is quite limited outside of Japan. We present a retrospective review of 18 patients at our center that received this therapy and describe their ultimate disposition. We observed that 39% of the population on hybrid dialysis ultimately transitioned to full in center HD, 28% continue until death, and 33% either transition to home HD or received a transplant. In our center, hybrid dialysis was successful as a bridging therapy or in balancing continuation of dialysis with quality of life among those with a limited prognosis.

New Insights Into Mechanisms of Acute Kidney Injury in Heart Disease.

Acute kidney injury is a frequent occurrence in patients with heart disease, and is associated with higher risk of adverse outcomes, including mortality. In the setting of decompensated heart failure, acute kidney injury can occur from hemodynamic and neurohormonal activation, venous congestion, and nephrotoxic medications. Certain medications, such as loop diuretics, renin angiotensin system blockers, and mineralocorticoid antagonists can seemingly cause acute kidney injury. However, this increase in creatinine level is not always associated with adverse outcomes and should be carefully differentiated so as to allow deliberate continuation of these cardio- and nephroprotective agents. In other settings such as cardiac surgery, acute kidney injury can occur from factors related to the cardiopulmonary bypass, renal hypoperfusion, or other perioperative factors. Last, patients with heart disease commonly undergo imaging procedures that require contrast administration. Contrast can indeed cause acute kidney injury, but these interventional procedures also can result in kidney injury from atheroembolic phenomena. This is well documented by the recent data reporting a higher risk of acute kidney injury from femoral compared with radial access. The advent of biomarkers of kidney injury present an opportunity for early detection, accurate differential diagnosis, as well as potentially designing innovative biomarker-enriched adaptive clinical trials.

Accurate GFR in obesity-protocol for a systematic review.

BACKGROUND: Obesity is increasing globally. Chronic kidney disease (CKD) is strongly associated with obesity. Kidney function is commonly estimated with equations using creatinine (such as CKD-EPI equation) which is a product of muscle metabolism. Decisions about categorizing CKD, planning modality of renal replacement therapies, and adjusting dosages of medications excreted by the kidneys are done using these equations. However, it is not well appreciated that creatinine-based equations may not accurately estimate kidney function in obese individuals. We plan a systematic review of diagnostic studies which will compare estimating equations to actual measured kidney function. METHODS: We will systematically search electronic bibliographic databases including MEDLINE, EMBASE, and the Cochrane Library with no restrictions on language or specific dates. The search terms will be adapted for the different databases using a combination of Medical Subject Heading and relevant keywords contained in titles and abstracts. Our preliminary search strategy using Cochrane, MEDLINE, and EMBASE databases have identified 190, 1246, and 1660 citations, respectively. For all studies selected, we will extract information on general study characteristics, study participant (age, sex, ethnicity, weight, height, BMI, BSA), type and protocol of reference standard utilized, the index test studied, the methodology of measurement of index test, categories of GFR, the proportion of eGFR within 10, 20, 30, 40, and 50% of measured GFR, and bias between eGFR and measured GFR. If the quality of methods and risk of bias are adequate, we will perform a meta-analysis. We will assess the heterogeneity using the χ 2 and the I 2 statistics to examine whether the estimates from studies included could be pooled. Sensitivity and multivariate meta-regression analyses will be performed to assess the effects of clinical factors and socio-demographic characteristics reported in included studies on the meta-analytic estimates. All analysis will be performed using the Comprehensive Meta-analysis software. DISCUSSION: This systematic review might help to inform clinicians on the best equation to use in patients with obesity and CKD for staging of CKD and for medication dosing. If no equation is deemed suitable, this review will form a basis for future studies of GFR in obese individuals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018104345.

Cloudy Dialysate as the Initial Presentation for Lymphoma.

Turbid dialysate in a patient on peritoneal dialysis is usually due to peritonitis and almost all these patients are started on empirical antibiotics pending cultures. However, in few of them with culture negative fluid, this could represent other etiologies like chyle, which requires more intensive investigations, and analysis of fluid itself reveals some rare diagnosis. We present one such report of chylous ascites with prompt investigation leading to a diagnosis of malignancy in a peritoneal dialysis patient.