Elevated Serum Potassium Research Articles

Early Post-transplant Renal Functions Predict Incidence of Acute Rejection in Kidney Transplantation

Objectives: After renal transplantation, a remarkable improvement of impaired patient’s kidney function is often observed. Preserving improved kidney function ensures long-term renal allograft survival. However, there are different risk factors; the acute rejection is the major risk factor. Therefore, the aim of the present study was to examine renal function within the first six months as independent variables in predicting long-term survival and incidence of acute rejection.
 Methods: Fifty-three patients who underwent kidney transplantation in 2016 and 2017 in King Abdulaziz Medical City- National Guard were evaluated consecutively1 and 2-month pre-transplant up to six months’ post-transplant. Time course of changes in kidney functions; measurements of serum creatinine (Scr), blood urea nitrogen(BUN), albumin, calcium, sodium and potassium were recorded. Estimated glomerular filtration rate (eGFR) and anion gap (AGAP) were also reported. In addition, age, anthropometric factors and causes of ESRD were analyzed.
 Results: Lower level of calcium was observed in 40% of patient’s two-month pre-transplantation and 69% of patients one month before. Normalization of calcium was achieved in all patients starting from second month post-transplantation. All patients presented elevated serum potassium level in pre-transplant months, however, renal transplant normalize potassium level starting from first month. A remarkable higher level of serum BUN was observed in all pre-transplant patients followed by dramatically decreased after renal transplant for first four months and remain in normal level starting from month 5. Likewise, serum creatinine was highly elevated in all pre-transplant patients. A profound reduction in serum creatinine started from month 1 post-transplant and normalizes at month 4. Moreover, both eGFR and AGAP were kept in normal level immediately after renal transplantation. All patients with early acute rejection during mean follow-up period have a remarkable elevated level of serum creatinine and profound decrease in eGFR starting from first month. While a significant higher level of serum BUN observed in fifth month only and serum albumin in third month.
 Conclusion: Significant elevation of serum creatinine and reduction in eGFR starting from first month were associated with post-transplanted patients with early acute rejection. The clinical use of eGFR and serum creatinine may aid in predicting incidence of early acute rejection.

Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis.

In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.

Hyperkalemic Cardiac Arrest in a Patient with Diabetic Ketoacidosis.

AimTo highlight the occurrence of cardiac arrest due to hyperkalemia in diabetic ketoacidosis (DKA).BackgroundDiabetic ketoacidosis is a commonly encountered condition. These patients can have normal or mildly elevated levels of potassium. Our patient had severe hyperkalemia due to DKA resulting in cardiac arrest. Her high potassium diet and use of angiotensin receptor blocker along with acute kidney injury (AKI) would have also contributed to hyperkalemia.Case descriptionA 58-year-old female, known case of diabetes mellitus on insulin therapy and hypertension on telmisartan, presented with nausea, vomiting, and abdominal pain. She was diagnosed to have DKA with AKI precipitated by missed insulin and urinary tract infection. She was also on high potassium diet. Her electrocardiogram showed sinus bradycardia with prolonged QRS interval. Her potassium levels were elevated. She soon went into asystole and cardiac arrest and was resuscitated. Diabetic ketoacidosis protocols were followed along with antibiotics, and the patient improved.ConclusionSevere hyperkalemia in DKA is uncommon, and this hyperkalemia resulting in cardiac arrest is an unreported scenario. Potassium correction along with DKA management protocol forms the mainstay of treatment.Clinical significanceMild to moderate elevation in serum potassium occurs frequently in DKA. However, severe hyperkalemia is uncommon and is likely to be the result of insulin deficiency, acidosis, hyperosmolality, severe dehydration, and renal potassium retention. Such elevated level of potassium requires urgent correction in order to prevent cardiac arrest.How to cite this articleManappallil RG, Nambiar J. Hyperkalemic Cardiac Arrest in a Patient with Diabetic Ketoacidosis. Indian J Crit Care Med 2020;24(8):737–738.

Insulin glucose infusion versus nebulised salbutamol versus combination of salbutamol and insulin glucose in acute hyperkalaemia in the emergency room: protocol for a randomised, multicentre, controlled study (INSAKA)

IntroductionHyperkalaemia is a common electrolyte disorder and can be life-threatening. In the emergency room (ER), interventions aim to protect patients from the immediate dangers of elevated serum potassium by redistributing...

P1531DIURETIC USE IN HEMODIALYSIS PATIENTS: BENEFIC ASSOCIATION WITH RESIDUAL RENAL FUNCTION AND ALL-CAUSE MORTALITY

Abstract Background and Aims In patients with end-stage renal disease (ESRD) on hemodialysis, the preservation of residual kidney function may result in a diversity of benefits in terms of survival and quality of life. The control of fluid and electrolyte homeostasis may play an important role in this setting. Elevated predialysis serum potassium is a common electrolyte disturbance that may worsen patient’s outcomes. Our aim was to study the impact of furosemide therapy in predialysis serum potassium levels, indicators of estimated residual renal function, and inflammatory markers, in ESRD patients under hemodialysis; moreover, we aimed to study the impact of furosemide-associated changes on mortality rate. Method A cross-sectional study was carried out on 289 adult patients on chronic dialysis therapy (hemodiafiltration and high flux hemodialysis). Patients were divided in 2 groups: the diuretic group (DG, n=116; 120.0 (IQR: 80-160) mg/daily median furosemide dose) and the non-diuretic group (NDG, n = 173), in which patients did not use furosemide. A large set of data was analyzed, encompassing hematological data, serum electrolyte parameters, inflammatory markers, dialysis adequacy, and biomarkers of residual kidney function. A 2-year follow up study was also performed by registering events of death (all-cause mortality). Results The DG patients, compared with NDG patients, presented: significantly lower predialysis serum potassium; more favorable blood biomarkers of kidney function - lower β-trace protein, cystatin C, creatinine and urea; greater residual glomerular filtration rate derived from equations with cystatin C, creatinine and creatinine–cystatin C; lower inflammation (significantly lower levels of high-sensitivity C-reactive protein); intradialytic ultrafiltration volume (L) was similar for the two groups. Mortality was significantly lower for DG patients, compared with NDG (13.6% versus 24.7%; P=0.029). Conclusion In ESRD patients under chronic dialysis, we found a significant association between current diuretic therapy and lower predialysis serum potassium levels, more favorable biomarkers of kidney function and a decreased inflammatory response that seem to contribute to a higher survival rate. Acknowledgments: The work was supported by UIDB/04378/2020 with funding from FCT/MCTES through national funds, by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).

Care Right Where You Are: Treating in Place to Avoid an Emergency Department Visit or Hospitalization

Care Right Where You Are: Treating in Place to Avoid an Emergency Department Visit or Hospitalization

PDB59 THE IMPACT OF HYPERKALAEMIA AND ITS CONCURRENCE WITH CARDIORENAL COMORBIDITIES ON HEALTHCARE RESOURCE USE IN THE UK

Hyperkalaemia (HK) is a potentially life-threatening electrolyte abnormality characterized by elevated serum potassium concentrations above 5.0mmol/L. The clinical and economic burden of HK is of concern for patients with cardiovascular and renal comorbidities. However, there is limited data on the impact of HK and its concurrence with comorbidities on healthcare resource use (HRU) in the UK. In this study we aimed to characterise HRU associated with HK hospitalisations in patients with different cardiovascular and renal comorbidities in the UK.

Rapid correction of hyperkalemia is associated with reduced mortality in ED patients

BackgroundHyperkalemia (HK) is common and associated with mortality. Our purpose was to determine if the rapid correction of elevated serum potassium level (K+) was associated with reduced mortality in emergency department (ED) patients. MethodsDesign: We reviewed the electronic medical records (EMR) of ED patients with HK (K+ ≥ 5.5 mEq/L) from 10/2016–10/2017. Setting: Large, academic ED. Participants: Adult ED patients presenting with hyperkalemia. Main outcomes and measures: The main outcome was in-hospital mortality. We compared outcomes of patients whose K+ normalized (dropped below 5.5 mEq/L) with those whose K+ did not normalize using chi-square and multivariate analyses to determine the associations between predictor variables and outcomes. ResultsFrom 114,977 ED visits, 1033 patients (0.9%, 95%CI 0.85–0.95%) had HK. Their mean (SD) age was 60 (26) years and 58% were male. Of these, 884 had a second K+ measured within a median (IQR) of 5 (3–8) hours. Mortality and admission rates were higher in patients with HK vs. those with normal K+ (8.5% vs. 0.8%, P < 0.001 and 80% vs. 39%, P < 0.001, respectively). Mortality was lower in patients whose HK normalized compared with those whose K+ remained elevated (6.3% vs. 12.7%, P = 0.001). After adjusting for age, creatinine, comorbidities, and initial K+, normalization of K+ was associated with reduced mortality (OR 0.47, 95%CI 0.28 to 0.80). ConclusionsNormalization of K+ during the ED stay in patients with HK is associated with a 50% mortality reduction. Efforts to rapidly identify and treat HK in the ED are needed.

Potassium-lowering agents for the treatment of nonemergent hyperkalemia: pharmacology, dosing and comparative efficacy.

Hyperkalemia represents a common and potentially life-threating electrolyte abnormality, a complication frequently observed in patients with heart failure, kidney disease, diabetes or in those receiving drug therapies influencing the renin-angiotensin-aldosterone system. Elevated serum potassium levels are often the result of impaired urinary potassium elimination, inadequate or reduced cellular potassium uptake, severe heart failure, use of medications influencing potassium levels in the circulation, or, more commonly, a combination of these factors. Strategies for the treatment of nonemergent hyperkalemia include the use of cation-exchange resins, polymers or other novel mechanisms of potassium trapping, including sodium polystyrene sulfonate, patiromer and sodium zirconium cyclosilicate. These agents differ in their pharmacology and mechanism of action, clinical efficacy, including onset and extent of potassium-lowering effect, dosage and administration, and potential safety and adverse effect profiles. In this review, an evaluation of these characteristics, including clinical evidence and safety concerns, in the management of nonemergent hyperkalemia will be explored.

Effects of enalapril and paricalcitol treatment on diabetic nephropathy and renal expressions of TNF-α, p53, caspase-3 and Bcl-2 in STZ-induced diabetic rats.

This study aimed to assess the renopreventive effect of enalapril and/or paricalcitol on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate their mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, p53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 μg/kg b.w. per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to significant decreases in the elevated serum urea, uric acid, creatinine, sodium and potassium levels; thereby reflecting the improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. The treatment with enalapril and paricalcitol in combination was the most potent in decreasing the elevated serum glucose levels. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine, TNF-α, and apoptotic mediators, p53 and caspase-3, were remarkably decreased in kidney of diabetic rats as a result of treatment while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol alone or in combination can prevent STZ diabetes-induced nephropathy through amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis. However, the treatment of diabetic rats with enalapril and paricalcitol in combination has no further significant improvement effects on renal function and damage when compared with enalapril or paclitaxel treated diabetic groups.

A per-protocol initiation of sacubitril/valsartan in an advanced heart failure disease management programme in the Middle East Gulf Region.

AimsThe aim of this study is to evaluate the utilization and success in therapy intensification after initiation of sacubitril/valsartan using a specified protocol within an advanced heart failure and transplant programme in the Middle East Gulf Region.Methods and resultsWe studied a single‐centre, retrospective cohort in a 364‐bedded multi‐speciality hospital located in the United Arab Emirates (February 2016 to July 2017). The advanced heart failure and transplant programme formulated an institutional protocol for initiation of sacubitril/valsartan with defined criteria for switching from angiotensin‐converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB). Prescribing this drug is intended for patients with heart failure with reduced ejection fraction with left ventricular ejection fraction ≤40%. We excluded patients (i) with age below 18 years or (ii) initiated on sacubitril/valsartan from an outside hospital with or without follow‐up in our outpatient clinic. We included 102 patients with an average initial dose of 78.9 ± 44.2 mg twice daily. Only 17 patients were on target doses of ACEI or ARB prior to switching to sacubitril/valsartan. Up‐titration was successful in 55 patients during the follow‐up period. In addition, 6.9% patients were hospitalized with heart failure exacerbation. In patients with elevated baseline serum potassium prior to initiating this medication, the serum potassium levels decreased post‐initiation by 0.5 ± 0.3 mmol/L (P = 0.0008).ConclusionsInitiating sacubitril/valsartan through a defined protocol selects for appropriate candidates and guides starting dose and titration. Overall, significant success can be achieved in replacing ACEI or ARB by sacubitril/valsartan in symptomatic heart failure with reduced ejection fraction patients.

Risk factors associated with resolution of diabetic ketoacidosis in pediatric critical care units

Objective: Diabetic ketoacidosis (DKA) is the main cause of morbidity and mortality in children with type-I Diabetes Mellitus. The goals of therapy are to correct dehydration, resolution of acidosis and fading of ketosis. Such serious complications necessitate closed monitoring of DKA patients with delicate, balanced therapy, probably at an intensive care facility. Regarding the fact that, each facility shoul determine the clinical profile of their own patient population, we aimed to investigate the risk factors for consequences and determine the timing of DKA resolution by analyzing the demographic and epidemiologic data, clinical outcome and the prognosis of diabetic ketoacidotic children admitted to PICU. Method: This descriptive, retrospective study was conducted in 105 children admitted to PICU with the complaints of DKA between January 2014 and December 2108. Demograhic data including age, gender, weight, height, body mass index (BMI), initial compliants with clinical findings and level of consciousness were recorded. Children were categorized into two groups depending on the timing of DM diagnosis (new onset of diabetes and established diabetes mellitus). DKA severity was determined by the degree of metabolic acidosis (mild, moderate, severe). SPSS-23 was used for statictics. Descriptive analyses were expressed as percentages, mean±standart deviation (SD), median with minimum and maximum values. Chi square and Fischer exact test were used for comparison of categorical variables. Student’s t-test, Mann Whitney U test and Wilcoxon rank sum test were assessed for continous variables. Pearson correlation coefficient and logistic regressions were used for correlations and to determine the risk factors. P-value < 0.05 was considered significant. Results: The patient demographics presented the mean age as 11.31±4.18 years, female/male ratio 1/1.4 and body mass index 18.48±4.48. Children were classified as mild DKA (29.5%), moderate DKA (35.2%) and severe DKA (35.2%) based on the acidosis severity. 48.6% of the patients had Kusmaull respiration; 30.5% had manifested altered consciousness. One patient had tomography-proven brain edema and had required mechanical ventilation due to neurological incapability to sustain airway Children with new onset of diabetes accounted for 51.4% of the study population. The mean age was 9.70±4.47 years; this group constituted a younger population compared the established DM patients (p<0.001). Altered mental state and kusmaull respiration also occurred at a higher rate and the major complaint seemed ae weight loss within two weeks (p=0.006, p=0.002, p<0.001 respectively). Children with established diabetes mellitus presented significant biochemical abnormalities in terms of elevated BUN and serum potassium levels (p<0.001, p<0.001); infections occurred as the major triggering factor for DKA at a rate of 80.4% at this group. We observed a positive correlation with DKA resolution with serum creatinine, calculated osmolality, anion gap (r=0.242, r=0.215, r=0.302) and a negative correlation with blood gas pH and HCO3 (r= -0.704, r= -0.694). In the multivariable regression model including age, gender, body mass index, PRISM-3 score, BUN, serum potassium, phosphate and chloride, only blood gas pH and new onset of diabetes appeared to be the independent risk factors for DKA resolution. 0.1 unit decrement in blood gas pH elongated the resolution by 3.76 hours (p<0.001, adjusted ratio: 0.743). New onset of diabetes mellitus also increased the length of resolution by 5.30 hours (p<0.001). Conclusions: Inıtial blood gas pH and presence of new onset of diabetes are the major risk factors in resolution of ketoacidosis.

Abstract P156: Kidney Function and Serum Potassium as Predictors of Spironolactone Initiation in Congestive Heart Failure

Introduction: There are a paucity of data on real-world spironolactone use among patients with congestive heart failure (CHF), and whether spironolactone initiation differs by kidney function and serum potassium. Hypothesis: Patients with reduced kidney function and elevated serum potassium are less likely to be prescribed spironolactone than patients with normal kidney function and serum potassium. Methods: We identified patient cohorts with incident CHF and available laboratory data in the Truven MarketScan Commercial Claims and Encounters database (MS) from 2010-2015 (N=22,881), and the Geisinger Health System Integrated Electronic Health Record (GHS) from 2004-2016 (N=17,470), and assessed medication use through prescription order and dispensing data, and comorbidities using ICD codes. We measured incidence, initial dose, and duration of incident spironolactone use, overall and by levels of kidney function and serum potassium. We used Cox proportional hazards regression models to quantify the association between measures of baseline and time-varying estimated glomerular filtration rate (eGFR) and serum potassium, and incident spironolactone use, adjusting for other medication use and comorbidities. Results: Among 22,881 incident CHF patients in the MS database, mean age at CHF was 54.3 (±8.7) years, 47.2% were female, and the mean eGFR was 78.9 ml/min/1.73m 2 (±21). The 17,470 incident CHF patients in GHS were older (74.0 years ±12.9), more likely to be female (51.5%), and have a lower mean eGFR (62.5 ±24.3). Both cohorts had a mean baseline serum potassium of 4.3 mEq/L (±0.5). There were 1,341 (1,774) incident prescriptions for spironolactone over 34,384 (52,187) person-years in MS (GHS). Median starting dose was 25 mg in both cohorts. Women were less likely to start spironolactone in both cohorts, while older patients were less likely to start spironolactone only in GHS. Compared to patients with eGFR &gt;90 ml/min/1.73m 2 , those with eGFR &lt;30 ml/min/1.73m 2 were less likely to initiate spironolactone in MS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.38-0.84) and GHS (HR = 0.69, CI: 0.48-0.99). Patients with serum potassium &lt;3.5 mEq/L were more likely to initiate spironolactone compared to those with 3.5-4.9 mEq/L (normal) in both cohorts (HR=1.99 [95% CI: 1.57-2.52] in MS; HR=2.70 [95% CI: 2.34-3.26] in GHS). Conclusion: Consistent with the labeled guidelines, patients with CHF and reduced kidney function were less likely to use spironolactone, while those with lower serum potassium levels were more likely to use spironolactone.

In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes

Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.

Severe suicidal self-poisoning with massive dose of potassium ferricyanide(III): hyperkalemia but not free cyanide may cause death

Potassium ferricyanide(III), K3[Fe(CN)6], has a widespread use in blueprint drawing, photography, chemical industry, and metallurgy. In mice, the oral lethal dose 50 (LD50) is 1600 mg kg−1. We report the case of a suicide attempt in a 37-year-old male by intentional ingestion of 80 g of potassium ferricyanide(III) dissolved in water. The estimated ingested dose was 770 mg kg−1. The patient reported vertigo as the first sign of poisoning and six episodes of diarrhea with dark-colored stool 2 h after ingestion. The patient was transported by ambulance to the intensive care unit 8 h after ingestion. He was conscious and spontaneously ventilating, with a Glasgow Coma Scale (GCS) score of 15. On ECG performed at admission, tall “tented” T waves in V3–V6 and progressive flattering of P waves were registered. Serum concentrations of potassium of 7.2 mmol dm−3, urea of 7.1 mmol dm−3, and creatinine of 162 µmol dm−3 indicated development of acute renal failure. Despite the administration of intravenous insulin and 10% glucose infusion during the first hours after admission, there was a further elevation of serum potassium to 7.4 mmol dm−3 suggesting acute renal failure. For this reason, intermittent hemodialysis was performed [duration 200 min, blood flow rate 147 cm3 min−1, online clearance monitoring (OCM) clearance rate 100 cm3 min−1, and substitution fluid volume 5.8 dm3]. The condition of the patient stabilized and he was discharged from hospital on the fourth day after admission. This case report demonstrates the risks of life-threatening hyperkalemia and acute renal failure as complications of massive ingestion of potassium ferricyanide(III).

Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective, observational cohort study

Lassa fever is a viral haemorrhagic disease endemic to west Africa. No large-scale studies exist from Nigeria, where the Lassa virus (LASV) is most diverse. LASV diversity, coupled with host genetic and environmental factors, might cause differences in disease pathophysiology. Small-scale studies in Nigeria suggest that acute kidney injury is an important clinical feature and might be a determinant of survival. We aimed to establish the demographic, clinical, and laboratory factors associated with mortality in Nigerian patients with Lassa fever, and hypothesised that LASV was the direct cause of intrinsic renal damage for a subset of the patients with Lassa fever. We did a retrospective, observational cohort study of consecutive patients in Nigeria with Lassa fever, who tested positive for LASV with RT-PCR, and were treated in Irrua Specialist Teaching Hospital. We did univariate and multivariate statistical analyses, including logistic regression, of all demographic, clinical, and laboratory variables available at presentation to identify the factors associated with patient mortality. Of 291 patients treated in Irrua Specialist Teaching Hospital between Jan 3, 2011, and Dec 11, 2015, 284 (98%) had known outcomes (died or survived) and seven (2%) were discharged against medical advice. Overall case-fatality rate was 24% (68 of 284 patients), with a 1·4 times increase in mortality risk for each 10 years of age (p=0·00017), reaching 39% (22 of 57) for patients older than 50 years. Of 284 patients, 81 (28%) had acute kidney injury and 104 (37%) had CNS manifestations and thus both were considered important complications of acute Lassa fever in Nigeria. Acute kidney injury was strongly associated with poor outcome (case-fatality rate of 60% [49 of 81 patients]; odds ratio [OR] 15, p<0·00001). Compared with patients without acute kidney injury, those with acute kidney injury had higher incidence of proteinuria (32 [82%] of 39 patients) and haematuria (29 [76%] of 38) and higher mean serum potassium (4·63 [SD 1·04] mmol/L) and lower blood urea nitrogen to creatinine ratio (8·6 for patients without clinical history of fluid loss), suggesting intrinsic renal damage. Normalisation of creatinine concentration was associated with recovery. Elevated serum creatinine (OR 1·3; p=0·046), aspartate aminotransferase (OR 1·5; p=0·075), and potassium (OR 3·6; p=0·0024) were independent predictors of death. Our study presents detailed clinical and laboratory data for Nigerian patients with Lassa fever and provides strong evidence for intrinsic renal dysfunction in acute Lassa fever. Early recognition and treatment of acute kidney injury might significantly reduce mortality. German Research Foundation, German Center for Infection Research, Howard Hughes Medical Institute, US National Institutes of Health, and World Bank.

QiDiTangShen Granules Reduced Diabetic Kidney Injury by Regulating the Phosphorylation Balance of the Tyrosine and Serine Residues of Insulin Receptor Substrate 1.

Background Diabetic nephropathy (DN) is a microvascular complication induced by diabetes mellitus (DM), which can affect life quality and long-term prognosis of patients with DM. Angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) are currently recommended for treating DN proteinuria, but patients receiving ACEI/ARB are at risk of elevated serum creatinine or potassium levels. Based on the “yin-yang” theory of traditional Chinese medicine, the present study explored the effect of QiDiTangShen (QDTS) granules on DN and the phosphorylation balance of tyrosine and serine residues of IRS-1. Methods In this experiment, db/db mice were used as an animal model for type 2 diabetic nephropathy. The intervention (QDTS granules and valsartan) started when the mice were 12 weeks old. C57BL/6 mice were used as normal control. The urine albumin excretion ratio (UAER) was measured by enzyme-linked immunosorbent assay (ELISA) before and after the intervention. The IRS-1, PI3K, Akt, and MAPK proteins expression and the phosphorylation levels were detected by western blot. Results QDTS granules reduced the 24-h urinary albumin excretion rate (UAE) in db/db mice with type 2 DM and attenuated the pathological changes of the kidney. QDTS granules also increased the activation level of the PI3K/Akt signaling pathway and reduced insulin resistance. In addition, QDTS granules inhibited the activation of ERK and p38MAPK and decreased the phosphorylation ratio of Ser307/Tyr896 of IRS-1 in renal tissue. Conclusions QDTS granules reduced DM-induced renal injury by improving insulin sensitivity via suppressing MAPK signaling and restoring the phosphorylation balance of tyrosine/serine of IRS-1.

The clinical significance of acute phase proteins and biochemical changes in sheep with acute ruminal acidosis

Acute ruminal acidosis is a common problem in ruminants that feed on high amount of concentrates and has been associated with inflammatory condition of the rumen and metabolic acidosis. The goals of this study were to measure the acute phase proteins (haptoglobin and C-reactive protein concentrations), and biochemical changes and to determine their association with the inflammatory condition and mortality in sheep with acute ruminal acidosis. A total of 25 sheep were included in this study and divided in to two groups [one group suffered from acute ruminal acidosis (n=15) and another control healthy group (n=10)]. Haptoglobin and C- reactive protein (CRP) concentrations were measured by turbidimetric immunoassays. While biochemical parameters were measured using spectrophotometric calorimetric methods. Haptoglobin concentrations were significantly higher in sheep with acute ruminal acidosis compared to control group (P &lt; 0.05). However, CRP were not statistically different between both group of sheep (P &gt; 0.05) Moreover, serum haptoglobin concentrations were higher in non-survivors sheep with acute ruminal acidosis compared to survivors (P &lt; 0.05). The likelihood of mortality was associated with elevated serum haptoglobin, lactate and potassium but also associated with low calcium and chloride concentrations in sheep with acute ruminal acidosis (P &lt; 0.05). In conclusion, haptoglobin concentrations were elevated in sheep with acute ruminal acidosis and could be considered more diagnostic and sensitive inflammatory biomarker than CRP in sheep with acute ruminal acidosis. Alterations of biochemical dynamics including lactate, electrolytes and minerals concentrations and energy metabolism could be involved in increased risk of non-survival in sheep with acute lactic acidosis.

Evaluation of the tolerability and efficacy of sodium polystyrene sulfonate for long-term management of hyperkalemia in patients with chronic kidney disease

Sodium polystyrene sulfonate (SPS) is a cation-exchanging resin that has been widely used for several decades as first-line therapy of mild chronic hyperkalemia in patients with chronic kidney disease (CKD). However, evidence to prove the long-term tolerability and efficacy of SPS for the treatment of this condition is still missing. In this retrospective, observational study, we enrolled 26 outpatients with stages 3-4 CKD who received oral therapy with low-dose SPS for mild chronic hyperkalemia in the Outpatient Nephrology clinic of our Department during 2010-2016. We obtained medical records on side effects potentially attributable to SPS use, and we analyzed the changes in serum electrolytes before and after the initiation of SPS therapy. Serum potassium levels fell from 5.9±0.4 to 4.8±0.5mmol/l (P<0.001) over a median follow-up of 15.4months (range 3-27months). SPS use was associated with a slight, but significant elevation in serum sodium levels (139.5±2.9 vs 141.2±2.4, P=0.006), whereas serum calcium and phosphate remained unchanged before and after the initiation of SPS. We recorded ten episodes of recurrent serum potassium elevation ≥5.5mmol/l, none of which required hospitalization or acute dialysis. No episode of colonic necrosis or any other serious drug-related adverse event was observed. SPS therapy was well-tolerated, since only 1 out of 26 patients discontinued SPS at 3months due to gastrointestinal intolerance. This study suggests that low-dose SPS is well-tolerated and can effectively normalize elevated serum potassium over several weeks in CKD outpatients with mild chronic hyperkalemia.

Nonsteroidal mineralocorticoid antagonists in diabetic kidney disease.

Current data highlight the pathological aspects of excess aldosterone in promoting glomerular hypertrophy, glomerulosclerosis, and proteinuria in diabetic kidney disease (DKD). The role of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in DKD is being evaluated in ongoing clinical trials. Recent studies demonstrate beneficial effects of adding MRAs to the treatment regimen of patients with type 2 diabetes with nephropathy. The MRAs spironolactone and eplerenone can protect against organ damage caused by elevated levels of serum aldosterone in patients with heart failure and DKD but are limited by their side effects, for example, hyperkalemia. Finerenone is more selective for the mineralocorticoid receptor than spironolactone and has greater affinity for the mineralocorticoid receptor than eplerenone. It reduces the concentration of aldosterone without causing significant elevation in serum potassium. MRAs have a clear role in reducing albuminuria when used with other renin-angiotensin system blockers in DKD; however, hyperkalemia limits their use. This article provides an overview of clinical studies with a novel MRA, finerenone, and several nonsteroidal MRAs being studied for treatment in DKD.