Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Potassium levels in women with polycystic ovary syndrome using spironolactone for long-term.

OBJECTIVE: Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term. DESIGN: Single-centre retrospective study. PATIENTS: Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time. MEASUREMENTS: Clinical and hormonal profiles before and during SPL treatment. RESULTS: Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50-150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1-5.5 mEq/L). CONCLUSIONS: The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.

Effect of preparation method for radioactive iodine therapy on serum electrolytes.

PURPOSE: Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT. MATERIALS AND METHODS: From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L). RESULTS: Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019). CONCLUSION: THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.

A randomized study to compare oral potassium binders in the treatment of acute hyperkalemia.

BACKGROUND: The KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy. METHODS: Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics). DISCUSSION: The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04585542 . Registered 14 October 2020.

The Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Outcomes of Patients Treated with Immune Checkpoint Inhibitors: a Retrospective Cohort Study.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the data on the response to treatment and tumour-based endpoints across different tumour types are unknown. MATERIALS AND METHODS: We carried out a retrospective study at two tertiary referral centres in Taiwan. All adult patients treated with ICIs between January 2015 and December 2021 were included. The primary outcome was overall survival and the secondary outcomes were progression-free survival (PFS) and clinical benefit rates. RESULTS: In total, 734 patients were enrolled in our study, of which 171 were RAASi users and 563 were non-users. Compared with non-users, RAASi users had a longer median overall survival [26.8 (interquartile range 11.3-not reached) versus 15.2 (interquartile range 5.1-58.4) months, P < 0.001] and PFS [12.2 (interquartile range 3.9-34.5) versus 5.0 (interquartile range 2.2-15.2) months, P < 0.001]. In univariate Cox proportional hazard analyses, the use of RAASi was associated with a 40% reduction in the risk of mortality [hazard ratio 0.58 (95% confidence interval 0.44-0.76), P < 0.001] and disease progression [hazard ratio 0.62 (95% confidence interval 0.50-0.77), P < 0.001]. The association remained significant after adjusting for underlying comorbidities and cancer therapy in multivariate Cox analyses. A similar trend was observed for PFS. Furthermore, RAASi users experienced a greater clinical benefit rate than non-users (69% versus 57%, P = 0.006). Importantly, the use of RAASi before ICI initiation was not associated with improved overall survival and PFS. RAASi were not associated with an increased risk of adverse events. CONCLUSION: The use of RAASi is associated with improved survival outcomes, treatment response and tumour-based endpoints in patients undergoing immunotherapy.

Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study.

INTRODUCTION: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown. METHODS: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up. RESULTS: After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI - 0.17 to 15.66; P = 0.055). CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.

Finerenone in diabetic kidney disease: A systematic review and critical appraisal.

BACKGROUND & AIMS: Finerenone is a novel non-steroidal mineralocorticoid antagonist (MRA) recently approved for the treatment of chronic kidney disease (CKD) in people with type 2 diabetes (T2D). We aim to conduct a systematic review of finerenone to know the efficacy and safety of finerenone in CKD with or without T2D. METHODS: A systematic search in the electronic database of PubMed and Google Scholar was made from inception until September 09, 2022, using several MeSH keywords related to finerenone. Ongoing trials were additionally searched from ClinicalTrials.Gov. RESULTS: Five phase 2 and three phase 3, randomized, double-blind, placebo- or active-controlled studies of finerenone have been published to date and several other randomized and real-world studies of finerenone are currently undergoing. CONCLUSIONS: In short-term studies in patients with CKD and reduced ejection heart failure, with or without T2D, finerenone 20 mg appears to have a better renal outcome compared with spironolactone and a better mortality outcome compared with eplerenone, with significantly lesser hyperkalemia compared to both spironolactone and finerenone. In long-term studies in patients with CKD and T2D, finerenone 10/20 mg significantly reduces the progression of renal disease and reduced CV endpoints (especially heart failure hospitalization) compared to placebo. Finerenone has no effect on HbA1c, body weight, and sexual side effects including gynecomastia, and has only a modest effect on blood pressure. However, hyperkalemia leading to drug withdrawal was significantly higher with finerenone compared to placebo. Safety data in real-world settings is a pressing priority.

Cardiorenal benefits of mineralocorticoid antagonists in CKD and type 2 diabetes : Lessons from the FIGARO-DKD trial.

Diabetic kidney disease (DKD) develops in almost half of all patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Despite the high risk of chronic renal failure in these patients, only few therapeutic strategies are available. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with DKD was established years ago and remains the hallmark of therapy. The past 2 years have seen a dramatic change in our therapeutic arsenal for CKD. Sodium-glucose co-transporter­2 inhibitors (SGLT2s) have been successfully introduced for the treatment of CKD. A further addition is a novel compound antagonizing the activation of the mineralocorticoid receptor: finerenone. Finerenone reduces albuminuria and surrogate markers of cardiovascular disease in patients who are already on optimal therapy. In the past, treatment with other mineralocorticoid receptor antagonists was hampered by a significantly increased risk of hyperkalemia. Finerenone had a much smaller effect on hyperkalemia. Together with a reduced effect on blood pressure and no signs of gynecomastia, this therapeutic strategy had a more specific anti-inflammatory effect and a smaller effect on the volume/electrolyte axis. In the FIDELIO-DKD study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of DKD and the incidence of cardiovascular events, with a relatively safe adverse event profile. In this article, we summarize the available evidence on the cardioprotective and nephroprotective effects of finerenone and analyze the molecular mechanisms involved. In addition, we discuss the potential future role of mineralocorticoid receptor inhibition in the treatment of patients with diabetic CKD.

Experience with the potassium binder patiromer in hyperkalaemia management in heart failure patients in real life.

AIMS: Hyperkalaemia (HK) is common in heart failure (HF) patients, related to renal dysfunction and medical treatment. It limits medical therapy optimization, which impacts prognosis. New potassium (K) binders help control HK, allowing better medical management of HF. METHODS AND RESULTS: A retrospective multicentre register included all outpatients with HF and HK (K ≥ 5.1 mEq/L) treated with patiromer according to current recommendations. We evaluated analytic and clinical parameters before starting the treatment and at 7, 30 and 90 days, as well as adverse events related to patiromer and treatment optimization. We included 74 patients (71.6% male) with a mean age of 70.8 years (SD 9.2). Sixty-seven patients (90.5%) presented HK in the previous year. Forty patients (54.1%) underwent down-titration of a renin-angiotensin-aldosterone inhibitor (RAASi) or a mineralocorticoid receptor antagonist (MRA), and 27 (36.5%) stopped any of them due to HK. Initial K was 5.5 mEq/L (SD 0.6), with a significantly reduction at 7 days (4.9 mEq/L (SD 0.8); P < 0.001), maintained at 90 days (4.9 mEq/L (SD 0.8); P < 0.001). There were no other electrolyte disturbances, with a slight improvement in renal function [glomerular filtration rate 39.6 mL/min (SD 20.4) to 42.7 mL/min (SD 23.2); P = 0.005]. Adverse events were reported in 33.9% of patients, the most common being hypomagnesaemia (16.3%), gastrointestinal disturbances (14.9%) and HK (2.8%). Withdrawal of patiromer was uncommon (12.2%) due to gastrointestinal disturbances in 66.7% of cases. Nine patients (12.2%) started on a RAASi, and 15 patients (20.3%) on an MRA during the follow-up. Forty-five patients (60.8%) increased the dose of RAASi or MRA, increasing to target doses in 5.4 and 10.8% of patients, respectively. At 90 days, NTproBNP values were reduced from 2509.5 pg/mL [IQR 1311-4,249] to 1396.0 pg/mL [IQR 804-4263]; P = 0.003, but the reduction was only observed in those who optimized HF medical treatment [NTproBNP from 1950.5 pg/mL (IQR 1208-3403) to 1349.0 pg/mL (IQR 804-2609); P < 0.01]. NYHA functional class only improved in 7.5% of patients, corresponding with those who optimized HF medical treatment. Compared with the previous 3 months before patiromer treatment, the rate of hospitalization was reduced from 28.4 to 10.9% (P < 0.01), and the emergency room visits from 18.9 to 5.4% (P < 0.01). CONCLUSIONS: In a real-life cohort of patients with HF, patiromer reduced and maintained K levels during 3 months of follow-up. The most common adverse events were hypomagnesaemia and gastrointestinal disturbances. Patiromer helps optimize medical treatment, increasing the percentage of patients treated with RAASi and MRA at target doses. At the end of follow-up, natriuretic peptides values and hospital visits were reduced, suggesting the benefit of optimizing HF medical treatment.

[Medical training and mini-Delphi approach to implement heart failure treatment with mineralocorticoid receptor antagonists]. / Training e mini-Delphi per implementare il trattamento dell'insufficienza cardiaca con gli antagonisti dei recettori dei mineralcorticoidi.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are a class of drugs still underused in heart failure with reduced ejection fraction. Hyperkalemia, worsening of renal function and gynecomastia are the main causes of the MRA missed prescription but also an inadequate knowledge of this class of drugs may represent a reason for their underuse. The aim of this project was to evaluate the possible usefulness of a unique and innovative web-based platform in order to identify the main issues related to the underuse of MRAs and to discuss shared strategies of interventions to overcome the obstacles to MRA prescription. METHODS: The "HF Clinical Practice project" enrolled 55 hospital cardiologists. It was based on the development and production of the eCaseTrack platform which was capable of activating a content-sharing system between professionals and specialists, using a mixed-methods study consisting of a survey, shared clinical experiences, training and consensus mini-Delphi method. RESULTS: The results of the survey showed that the respondents substantially agreed about the criteria for MRA prescription (NYHA class, left ventricular ejection fraction, glomerular filtration rate and serum potassium). This agreement was confirmed by mini-Delphi, by which the use of MRAs in patients with hypotension, hyperkalemia and gynecomastia emerged as the most controversial issue. CONCLUSIONS: A web-based system of sharing clinical experiences and discussing controversial issues, is useful to implement the introduction of a proven efficacious therapeutic strategy which is still underused in current clinical practice.

Renal events in patients receiving neprilysin inhibitors: a systematic review and meta-analysis.

BACKGROUND: While it is well known that angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe sacubitril/valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared with ACEi or ARBs. METHODS: We performed a systematic meta-analysis including 17 randomized controlled trials (study drug sacubitril/valsartan or omapatrilat), involving a total of 23 569 patients, after searching PubMed, Cochrane, ClinicalTrials.org and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia, were extracted. Pooled odds ratios (ORs) were calculated using the DerSimonian and Laird method. The study was registered at PROSPERO. RESULTS: Overall, treatment with sacubitril/valsartan or omapatrilat showed a slightly lower risk of any renal event [OR 0.82 (0.7-0.97)] compared with treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events [OR 0.8 (0.69-0.93)] and a decrease in estimated glomerular filtration rate decline [mean difference -0.58 mL/min (-0.83 to -0.33 mL/min)]. There was no difference in chronic renal events [OR 0.92 (0.8-1.05)] or hyperkalemia [OR 1.02 (0.84-1.23)]. CONCLUSION: NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of NEPi on decreasing progression of CKD.

Consensus on the management of hyperkalemia in patients with heart failure: Recommendations from the SEC-SEMI.

Use of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) and reduced ejection fraction is associated with functional improvement, an increase in perceived quality of life, a reduction in the probability of cardiovascular death, and a decrease in the number of hospitalizations. Some of these drugs are also efficacious in patients with chronic kidney disease and albuminuria as well as in patients with resistant hypertension. Despite their numerous benefits, RAASi are associated with an increase in incidence of hyperkalemia, especially in patients with concomitant chronic kidney disease. Hyperkalemia is a common electrolyte disorder that is defined as an elevation in plasma concentrations of potassium above 5 mEq/L. It has been related to rehospitalizations, malignant arrhythmias, and an increase in mortality. On the other hand, optimized treatment with RAASi requires progressive dose increases which can in turn entail a greater probability of hyperkalemia. For all of these reasons, it is necessary to establish management and treatment guidelines for these patients. This consensus document arises from this objective. Its recommendations have been developed by a group of ten experts and reviewed by a panel of another ten specialists in the treatment of patients with HF (ten cardiologists and ten internists in total). This document has been endorsed by the Spanish Society of Cardiology (SEC, for its initials in Spanish) and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).

Observational study of the relative efficacy of insulin-glucose treatment for hyperkalaemia in patients with liver cirrhosis.

OBJECTIVES: To determine if liver cirrhosis is associated with reduced efficacy of insulin-glucose treatment in moderate to severe hyperkalaemia. DESIGN: Retrospective, cohort study. SETTING: Two secondary and one tertiary care hospital at a large metropolitan healthcare network in Melbourne, Australia. PARTICIPANTS: This study included 463 adults with a mean age of 68.7±15.8 years, comprising 79 patients with cirrhosis and 384 without cirrhosis as controls, who received standard insulin-glucose treatment for a serum potassium ≥6.0 mmol/L from October 2016 to March 2020. Patients were excluded if they received an insulin infusion, or if there was inadequate follow-up data for at least 6 hours after IDT due to death, lost to follow-up or inadequate biochemistry monitoring. The mean Model for End-stage Liver Disease score in patients with cirrhosis was 22.2±7.5, and the distribution of the Child-Pugh score for cirrhosis was: class A (24%), class B (46%), class C (30%). OUTCOME MEASURES: The primary outcome was the degree of potassium lowering and the secondary outcome was the proportion of patients who achieved normokalaemia, within 6 hours of treatment. RESULTS: The mean pretreatment potassium for the cohort was 6.57±0.52 mmol/L. After insulin-glucose treatment, mean potassium lowering was 0.84±0.58 mmol/L in patients with cirrhosis compared with 1.33±0.75 mmol/L for controls (p<0.001). The proportion of patients achieving normokalaemia was 33% for patients with cirrhosis, compared with 53% for controls (p=0.001). By multivariable regression, on average, liver cirrhosis was associated with a reduced potassium lowering effect of 0.42 mmol/L (95% CI 0.22 to 0.63 mmol/L, p<0.001) from insulin-glucose treatment, after adjusting for age, serum creatinine, cancer, pretreatment potassium level, ß-blocker use and cotreatments (sodium polystyrene sulfonate, salbutamol, sodium bicarbonate). CONCLUSIONS: Our observational data suggest reduced efficacy of insulin-glucose treatment for hyperkalaemia in patients with cirrhosis.

Effects of estimated glomerular filtration rate and diabetes mellitus on the effect of insulin for treating hyperkalemia during anesthesia.

PURPOSE: We analyzed the effectiveness of insulin for treating hyperkalemia (≥ 5 mEq/L) during anesthesia and the effects of the estimated glomerular filtration rate (eGFR) and diabetes mellitus (DM) on the insulin treatment. METHODS: Patients 18 years of age and older who received intravenous insulin lispro for hyperkalemia under general anesthesia between January 2010 and March 2020 were enrolled. We performed three propensity score matching analyses according to eGFR stages (eGFR ≥ 60 vs. 30 ≤ eGFR < 60 and eGFR ≥ 60 vs. eGFR < 30 mL/min/1.73 m2) and DM status. RESULTS: The study included 475 patients. For patients with hyperkalemia during surgery, the odds ratios [ORs] of failure to decrease potassium (K+) after insulin treatment were higher in patients with eGFR < 30 mL/min/1.73 m2 (adjusted OR 3.24; 95% confidence interval 1.38-7.64; P = 0.007) than in patients with eGFR ≥ 60 mL/min/1.73 m2. There was no significant difference in the ORs of patients with 30 ≤ eGFR < 60 mL/min/1.73 m2 and DM. CONCLUSION: The patients with a low eGFR had a higher incidence of K+ not decreasing after insulin treatment. Periodic assessment of K+ may be required during anesthesia.

SPS(Kayexalate)/CPS(K-Bind) crystals in the gastrointestinal tract-An experience from a tertiary center.

INTRODUCTION: Kayexalate (Sodium Polystyrene Sulfonate/SPS) and K-bind (Calcium Polystyrene Sulfonate/CPS) are cation exchange resins, commonly used for treatment of hyperkalaemia. SPS/CPS induced injury of the gastrointestinal tract(GIT) is rare, can be potentially life threatening but is under-recognized. This study aims to increase awareness of pathologists and clinicians of this under-reported complication of a drug commonly used to treat hyperkalaemia. MATERIALS: Study population comprised patients with SPS/CPS (Kayexalate or its analogues) crystals identified in gastrointestinal specimens from 2017-2019 at a tertiary care centre. Clinical details, relevant investigations, imaging and endoscopic findings, patient follow up details were obtained from the hospital electronic information system. RESULTS: A total of 10 patients with SPS/ CPS crystals in the GIT were encountered over 2 years. Male to female ratio was 9:1, with mean age 66.5years (range 52-82 years). Eight cases were mucosal biopsies and 2 were resection specimens. Additional pathology (tumours, colonic perforation) was present in 80% of patients. The characteristic morphological appearance of the CPS/SPS crystals on H&E stains were supported by special stains -Periodic acid Schiff(PAS) and Acid fast Bacilli(AFB). In all cases, the treatment history with SPS/CPS for hyperkalaemia was obtained only after the histological examination. Most common etiology of hyperkalaemia encountered was chronic kidney disease(CKD)/ Acute on chronic kidney disease. CONCLUSION: It is important for pathologists to recognise the presence of these crystals especially in small biopsies as early feedback to clinicians can help in appropriate management and avoidance of more serious adverse outcome. To the best of our knowledge, this is the first series of 10 consecutive cases of SPS/CPS crystals encountered in gastrointestinal tract to be reported from India.

Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

The Association of Insulin-dextrose Treatment with Hypoglycemia in Patients with Hyperkalemia.

Treatment of hyperkalemia with intravenous insulin-dextrose is associated with a risk of hypoglycemia. We aimed to determine the factors associated with hypoglycemia (glucose < 3.9 mmol/L, or < 70 mg/dL) and the critical time window with the highest incidence. In a retrospective cohort study in a tertiary hospital network, we included 421 adult patients with a serum potassium ≥ 6.0 mmol/L who received insulin-dextrose treatment. The mean age was 70 years with 62% male predominance. The prevalence of diabetes was 60%, and 70% had chronic kidney disease (eGFR < 60 ml/min/1.73 m2). The incidence of hypoglycemia was 21%. In a multivariable logistic regression model, the factors independently associated with hypoglycemia were: body mass index (per 5 kg/m2, OR 0.85, 95% CI: 0.69-0.99, P = 0.04), eGFR < 60 mL/min/1.73 m2 (OR 2.47, 95% CI: 1.32-4.63, P = 0.005), diabetes (OR 0.57, 95% CI 0.33-0.98, P = 0.043), pre-treatment blood glucose (OR 0.84, 95% CI: 0.77-0.91, P < 0.001), and treatment in the emergency department compared to other locations (OR 2.53, 95% CI: 1.49-4.31, P = 0.001). Hypoglycemia occurred most frequently between 60 and 150 min, with a peak at 90 min. Understanding the factors associated with hypoglycemia and the critical window of risk is essential for the development of preventive strategies.

Kayexalate-induced colitis and rectal stricture.

A 57-year-old man underwent emergency laparoscopic loop colostomy for acute recto-sigmoid obstruction. He was hospitalised 2 months previously, at another facility for diabetic ketoacidosis (DKA) and hyperkalaemia. He had no gastrointestinal symptoms prior to the hospitalisation. Both surgical exploration and intraoperative sigmoidoscopy showed ulcerations of sigmoid colon and proximal rectum with a pinhole stricture in mid-rectum. After ruling out all aetiologies, and due to persistence of the colonic ulcerations on a follow-up colonoscopy, a diagnosis of Crohn's colitis was made, and the patient was started on infliximab and 6-mercaptopurine (6-MP). Six months later, on rereview of all the biopsies, it was noted that a key element of presence of crystals suggestive of Kayexalate on the initial colorectal biopsies was missed. It was later found out that the patient had received rectal Kayexalate for treatment of DKA at the other facility. Hence, infliximab and 6-MP were both discontinued. All the colonoscopies, following the discontinuation of the medications, showed complete resolution of colitis but persistence of the mid-rectum stricture. This was treated with a fully covered metal stent for 12 weeks with only partial improvement of the stricture. He was hence referred for ultra-low anterior resection of rectum and take down of colostomy.

Hyperkalemia in chronic kidney disease

SUMMARY Hyperkalemia is a frequent finding in patients with chronic kidney disease (CKD). This increase in serum potassium levels is associated with decreased renal ion excretion, as well as the use of medications to reduce the progression of CKD or to control associated diseases such as diabetes mellitus and heart failure. Hyperkalemia increases the risk of cardiac arrhythmia episodes and sudden death. Thus, the control of potassium elevation is essential for reducing the mortality rate in this population. Initially, the management of hyperkalemia includes orientation of low potassium diets and monitoring of patients' adherence to this procedure. It is also important to know the medications in use and the presence of comorbidities to guide dose reduction or even temporary withdrawal of any of the potassium retention-related drugs. And finally, the use of potassium binders is indicated in both acute episodes and chronic hyperkalemia.

RESUMO A hiperpotassemia é um achado frequente em pacientes com doença renal crônica (DRC). Esta elevação do nível sérico de potássio está associada à diminuição da excreção renal do íon, assim como ao uso de medicações para retardar a progressão da DRC ou para controlar doenças associadas, como diabetes mellitus e insuficiência cardíaca. A hiperpotassemia aumenta o risco de episódios de arritmia cardíaca e morte súbita. Assim, o controle da elevação de potássio é essencial para a diminuição da taxa de mortalidade nessa população. O manejo da hiperpotassemia inclui, inicialmente, orientação de dietas com baixo teor de potássio e acompanhamento da aderência dos pacientes a esse procedimento. Também é importante conhecer as medicações em uso e a presença de comorbidades, a fim de orientar a redução de doses ou até mesmo a suspensão temporária de alguma das drogas relacionadas à retenção de potássio. E, finalmente, o uso de quelantes de potássio é indicado tanto em episódios agudos como nos casos de hiperpotassemia crônica.