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American Family Physician Dec 2019Acute kidney injury is a clinical syndrome characterized by a rapid decline in glomerular filtration rate and resultant accumulation of metabolic waste products. Acute...
Acute kidney injury is a clinical syndrome characterized by a rapid decline in glomerular filtration rate and resultant accumulation of metabolic waste products. Acute kidney injury is associated with an increased risk of mortality, cardiovascular events, and progression to chronic kidney disease. Severity of acute kidney injury is classified according to urine output and elevations in creatinine level. Etiologies of acute kidney injury are categorized as prerenal, intrinsic renal, and postrenal. Accurate diagnosis of the underlying cause is key to successful management and includes a focused history and physical examination, serum and urine electrolyte measurements, and renal ultrasonography when risk factors for a postrenal cause are present (e.g., older male with prostatic hypertrophy). General management principles for acute kidney injury include determination of volume status, fluid resuscitation with isotonic crystalloid, treatment of volume overload with diuretics, discontinuation of nephrotoxic medications, and adjustment of prescribed drugs according to renal function. Additional supportive care measures may include optimizing nutritional status and glycemic control. Pharmacist-led quality-improvement programs reduce nephrotoxic exposures and rates of acute kidney injury in the hospital setting. Acute kidney injury care bundles are associated with improved in-hospital mortality rates and reduced risk of progression. Nephrology consultation should be considered when there is inadequate response to supportive treatment and for acute kidney injury without a clear cause, stage 3 or higher acute kidney injury, preexisting stage 4 or higher chronic kidney disease, renal replacement therapy, and other situations requiring subspecialist expertise.
Topics: Acute Kidney Injury; Creatinine; Fluid Therapy; Glomerular Filtration Rate; Humans; Nephrology; Prognosis; Referral and Consultation; Risk Factors
PubMed: 31790176
DOI: No ID Found -
Advances in Therapy Nov 2023The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2)...
INTRODUCTION
The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors.
METHODS
In this multicenter, open-label, prospective, interventional study, esaxerenone was started at 1.25 or 2.5 mg/day and could be gradually increased to 5 mg/day on the basis of blood pressure (BP) and serum potassium levels. Oral hypoglycemic or antihypertensive medications prior to obtaining consent was continued. Data were evaluated in the total population and creatinine-based estimated glomerular filtration rate (eGFR) subcohorts (eGFR ≥ 60 mL/min/1.73 m [G1-G2 subcohort] and 30 to < 60 mL/min/1.73 m [G3 subcohort]).
RESULTS
In total, 93 patients were evaluated (G1-G2, n = 49; G3, n = 44). Morning home systolic/diastolic BP values (SBP/DBP) were significantly reduced from baseline to week 12 (- 11.8 ± 10.8/- 5.1 ± 6.3 mmHg, both P < 0.001) and week 24 (- 12.9 ± 10.5/- 5.7 ± 6.3 mmHg, both P < 0.001). Similar results were observed in both eGFR subcohorts. The urinary albumin-to-creatinine ratio significantly decreased from baseline to week 24 in the total population (geometric percentage change, - 49.1%, P < 0.001) and in both eGFR subcohorts. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 45.2% and 12.9%, respectively; most were mild or moderate. Serum potassium levels increased over the first 2 weeks of esaxerenone treatment, gradually decreased by week 12, and remained constant to week 24. One patient in the G1-G2 subcohort had serum potassium levels ≥ 5.5 mEq/L. No patients had serum potassium ≥ 6.0 mEq/L.
CONCLUSION
Esaxerenone effectively lowered BP, was safe, and showed renoprotective effects in hypertensive patients with diabetes mellitus receiving treatment with SGLT2 inhibitors. Esaxerenone and SGLT2 inhibitors did not interfere with either drug's efficacy and may reduce the frequency of serum potassium elevations, suggesting they are a compatible combination.
CLINICAL TRIAL REGISTRATION
jRCTs031200273.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Creatinine; Prospective Studies; Hypertension; Blood Pressure; Diabetes Mellitus, Type 2; Potassium; Glucose; Sodium
PubMed: 37733211
DOI: 10.1007/s12325-023-02633-8 -
Iranian Journal of Kidney Diseases Jul 2008In situations where the cause of hypokalemia is not obvious, measurement of urinary potassium excretion and blood pressure and assessment of acid-base balance are often...
In situations where the cause of hypokalemia is not obvious, measurement of urinary potassium excretion and blood pressure and assessment of acid-base balance are often helpful. A random urine potassium-creatinine ratio (K/C) less than 1.5 suggests poor intake, gastrointestinal losses, or a shift of potassium into cells. If hypokalemia is associated with paralysis, we should consider hyperthyroidism, familial or sporadic periodic paralysis. Metabolic acidosis with a urine K/C ratio less than 1.5 suggests lower gastrointestinal losses due to diarrhea or laxative abuse. Metabolic acidosis with K/C ratio of 1.5 higher is often due to diabetic ketoacidosis or type 1 or type 2 distal renal tubular acidosis. Metabolic alkalosis with a K/C ratio less than 1.5 and a normal blood pressure is often due to surreptitious vomiting. Metabolic alkalosis with a higher K/C ratio and a normal blood pressure suggests diuretic use, Bartter syndrome, or Gitelman syndrome. Metabolic alkalosis with a high urine K/C ratio and hypertension suggests primary hyperaldosteronism, Cushing syndrome, congenital adrenal hyperplasia, renal artery stenosis, apparent mineralocorticoid excess, or Liddle syndrome. Hypomagnesemia can lead to increased urinary potassium losses and hypokalemia. The differential rests upon measurement of blood magnesium, aldosterone and renin levels, diuretic screen in urine, response to spironolactone and amiloride, measurement of plasma cortisol level and the urinary cortisol-cortisone ratio, and genetic testing.
Topics: Acid-Base Imbalance; Algorithms; Creatinine; Humans; Hypertension; Hypokalemia; Potassium
PubMed: 19377223
DOI: No ID Found -
Urinary Albumin-to-Creatinine Ratio in Normal Range, Cardiovascular Health, and All-Cause Mortality.JAMA Network Open Dec 2023Although cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of...
IMPORTANCE
Although cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of mortality, few studies have investigated whether cardiovascular health (CVH) modifies the harmful outcomes of high-normal UACR.
OBJECTIVE
To investigate associations of traditionally normal UACR and CVH with all-cause mortality.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used National Health and Nutrition Examination Survey data from 2005 through 2018 and linked mortality information until 2019. Data were analyzed from March 1 through October 31, 2023. The study included adult participants aged 20 to 79 years with a normal UACR (<30 mg/g) based on Kidney Disease: Improving Global Outcomes criteria.
EXPOSURES
The UACR was treated as a continuous variable and categorized into tertiles delineated as low (<4.67 mg/g), medium (4.67-7.67 mg/g), and high (7.68 to <30 mg/g). Cardiovascular health was assessed using Life's Essential 8 scores and grouped as poor (0-49 points), moderate (50-79 points), and ideal (80-100 points).
MAIN OUTCOMES AND MEASURES
Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of UACR with all-cause mortality in total participants and as stratified by CVH groups.
RESULTS
The study included 23 697 participants (mean [SD] age, 45.58 [15.44] years; 11 806 women [49.7%] and 11 891 men [50.3%]). During the median 7.8 years (range, 4.5-11.1 years) of follow-up, 1403 deaths were recorded. Near-linear associations were observed for continuous UACR and CVH with all-cause mortality. Compared with the low UACR group, high UACR in the normal range showed an increased mortality risk in the moderate and poor CVH groups (CVH [50-79]: HR, 1.54 [95% CI, 1.26-1.89]; CVH [0-49]: HR, 1.56 [95% CI, 1.10-2.20]), with a significant multiplicative interaction of UACR and CVH (P < .001).
CONCLUSIONS AND RELEVANCE
The findings suggest that high UACR within the normal range is associated with a significantly increased risk of all-cause mortality, with the association more pronounced in adults with poor CVH status. These findings highlight the importance of risk management for early kidney dysfunction, particularly among individuals with poor CVH.
Topics: Adult; Male; Humans; Female; Middle Aged; Cardiovascular Diseases; Creatinine; Cohort Studies; Nutrition Surveys; Reference Values; Follow-Up Studies; Albumins
PubMed: 38113044
DOI: 10.1001/jamanetworkopen.2023.48333 -
Journal of Neuroinflammation Feb 2023Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We...
BACKGROUND
Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.
METHODS
CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and gut-derived uremic toxins on brain microvascular endothelial barrier.
RESULTS
CKD was induced in aged C57BL/6J mice with significant increases in both serum creatinine and cystatin C levels (p < 0.0001) without elevation of systolic or diastolic blood pressure. CMH was significantly increased and positively correlated with serum creatinine level (Spearman r = 0.37, p < 0.01). Moreover, CKD significantly increased Iba-1-positive immunoreactivity by 51% (p < 0.001), induced a phenotypic switch from resting to activated microglia, and enhanced fibrinogen extravasation across the blood-brain barrier (BBB) by 34% (p < 0.05). On analysis stratified by sex, the increase in CMH number was more pronounced in male mice and this correlated with greater creatinine elevation in male compared with female mice. Microglial depletion with PLX3397 diet significantly decreased CMH formation in CKD mice without affecting serum creatinine levels. Incubation of CKD serum significantly reduced transendothelial electrical resistance (TEER) (p < 0.01) and increased sodium fluorescein permeability (p < 0.05) across the endothelial monolayer. Uremic toxins (i.e., indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide) in combination with urea and lipopolysaccharide induced a marked drop in TEER compared with the control group (p < 0.0001).
CONCLUSIONS
CKD promotes the development of CMH in aged mice independent of blood pressure but directly proportional to the degree of renal impairment. These effects of CKD are likely mediated in part by microglia and are associated with BBB impairment. The latter is likely related to gut-derived bacteria-dependent toxins classically associated with CKD. Overall, these findings demonstrate an important role of CKD in the development of cerebral small vessel disease.
Topics: Animals; Female; Male; Mice; Brain; Creatinine; Mice, Inbred C57BL; Renal Insufficiency, Chronic; Uremic Toxins; Intracranial Hemorrhages
PubMed: 36841828
DOI: 10.1186/s12974-023-02703-2 -
Journal of Cachexia, Sarcopenia and... Aug 2022Muscle wasting is prevalent in cancer patients, and early recognition of this phenomenon is important for risk stratification. Recent studies have suggested that the...
BACKGROUND
Muscle wasting is prevalent in cancer patients, and early recognition of this phenomenon is important for risk stratification. Recent studies have suggested that the creatinine-cystatin C ratio may correlate with muscle mass in several patient populations. The association between creatinine-cystatin C ratio and survival was assessed in cancer patients.
METHODS
A total of 3060 patients who were evaluated for serum creatinine and cystatin C levels at the time of cancer diagnosis were included. The primary outcome was 6-month mortality. The 1-year mortality, and length of intensive care unit (ICU) and hospital stay were also evaluated.
RESULTS
The mean age was 61.6 ± 13.5 years, and 1409 patients (46.0%) were female. The median creatinine and cystatin C levels were 0.9 (interquartile range [IQR], 0.6-1.3) mg/dL and 1.0 (IQR, 0.8-1.5) mg/L, respectively, with a creatinine-cystatin C ratio range of 0.12-12.54. In the Cox proportional hazards analysis, an increase in the creatinine-cystatin C ratio was associated with a significant decrease in the 6-month mortality (per 1 creatinine-cystatin C ratio, hazard ratio [HR] 0.35; 95% confidence interval [CI], 0.28-0.44). When stratified into quartiles, the risk of 6-month mortality was significantly lower in the highest quartile (HR 0.30; 95% CI, 0.24-0.37) than in the lowest quartile. Analysis of 1-year mortality outcomes revealed similar findings. These associations were independent of confounding factors. The highest quartile was also associated with shorter lengths of ICU and hospital stay (both P < 0.001).
CONCLUSIONS
The creatinine-cystatin C ratio at the time of cancer diagnosis significantly associates with survival and hospitalization in cancer patients.
Topics: Aged; Creatinine; Cystatin C; Female; Humans; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Retrospective Studies
PubMed: 35478277
DOI: 10.1002/jcsm.13006 -
International Journal of Environmental... Dec 2022Increasingly popular, ultra-endurance participation exposes athletes to extremely high levels of functional and structural damage. Ultra-endurance athletes commonly... (Review)
Review
Increasingly popular, ultra-endurance participation exposes athletes to extremely high levels of functional and structural damage. Ultra-endurance athletes commonly develop acute kidney injury (AKI) and other pathologies harmful to kidney health. There is strong evidence that non-steroidal anti-inflammatory drugs, common amongst ultra-athletes, is linked to increased risk and severity of AKI and potentially ischaemic renal injury, i.e., acute tubular necrosis. Ultra-endurance participation also increases the risk of exertional rhabdomyolysis, exercise-associated hyponatremia, and gastrointestinal symptoms, interlinked pathologies all with potential to increase the risk of AKI. Hydration and fuelling both also play a role with the development of multiple pathologies and ultimately AKI, highlighting the need for individualised nutritional and hydration plans to promote athlete health. Faster athletes, supplementing nitrates, and being female also increase the risk of developing AKI in this setting. Serum creatinine criteria do not provide the best indicator for AKI for ultra-athletes therefore further investigations are needed to assess the practicality and accuracy of new renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL). The potential of recurring episodes of AKI provide need for further research to assess the longitudinal renal health impact of ultra-participation to provide appropriate advice to athletes, coaches, medical staff, and event organisers.
Topics: Humans; Female; Male; Acute Kidney Injury; Kidney; Exercise; Hyponatremia; Nutritional Status; Biomarkers; Creatinine
PubMed: 36554767
DOI: 10.3390/ijerph192416887 -
Chest Jun 2012Identifying patients with impaired renal function is crucial in the setting of critical illness. Serum creatinine serves as the gold standard for assessing steady-state... (Review)
Review
Identifying patients with impaired renal function is crucial in the setting of critical illness. Serum creatinine serves as the gold standard for assessing steady-state renal function, helping to define those with chronic kidney disease (CKD). Although these baseline creatinine values are often not available in the setting of critical illness, CKD, whether defined by serum creatinine or proteinuria, increases the risk of developing acute kidney injury (AKI). Despite delays in elevations following renal insults, serum creatinine remains the standard for assessing acute changes in renal function. Standardized definitions of AKI, using changes in serum creatinine and urine output, have informed the epidemiology of ICU-acquired AKI and have helped define the long-term outcomes in patients who experience AKI. A complex cyclical interplay exists between AKI and CKD, in which CKD predisposes patients to an increased risk of AKI, whereas those with AKI, regardless of baseline renal function, are more likely to suffer from post-AKI CKD. The clarification of the AKI-CKD dynamic remains a work in progress and will be aided by the implementation of novel measures of renal function. Several novel biomarkers of renal function have been proposed to augment serum creatinine in the diagnosis of AKI and CKD. These biomarkers, taken with recent clinical investigations, have laid the groundwork for the impending paradigm shift in risk stratifying and in diagnosing changes in renal function in the ICU.
Topics: Biomarkers; Creatinine; Glomerular Filtration Rate; Humans; Intensive Care Units; Kidney Function Tests; Proteinuria; Renal Insufficiency; Risk Factors; Urinalysis
PubMed: 22670020
DOI: 10.1378/chest.11-1513 -
Nephron 2015The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding... (Review)
Review
BACKGROUND/AIMS
The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding the impact of AKI between settings is limited by heterogeneity in the selection of reference creatinine to anchor the definition of AKI. In this mini-review, we discuss different approaches used to select reference creatinine and their relative merits and limitations.
METHODS
We reviewed the literature to obtain representative examples of published baseline creatinine definitions when pre-hospital data were not available, as well as literature evaluating the estimation of baseline renal function, using PubMed and reference back-tracing within known works.
RESULTS
(1) Pre-hospital creatinine values are useful in determining reference creatinine, and in high-risk populations, the mean outpatient serum creatinine value 7-365 days before hospitalization closely approximates nephrology adjudication, (2) in patients without pre-hospital data, the eGFR 75 approach does not reliably estimate true AKI incidence in most at-risk populations, (3) using the lowest inpatient serum creatinine may be reasonable, especially in those with preserved kidney function, but may generously estimate AKI incidence and severity and miss community-acquired AKI that does not fully resolve, (4) using more specific definitions of AKI (e.g., KIDGO stages 2 and 3) may help to reduce the effects of misclassification when using surrogate values and (5) leveraging available clinical data may help refine the estimate of reference creatinine.
CONCLUSIONS
Choosing reference creatinine for AKI calculation is important for AKI classification and study interpretation. We recommend obtaining data on pre-hospital kidney function, wherever possible. In studies where surrogate estimates are used, transparency in how they are applied and discussion that informs the reader of potential biases should be provided. Further work to refine the estimation of reference creatinine is needed.
Topics: Acute Kidney Injury; Biomarkers; Creatinine; Humans; Kidney Function Tests
PubMed: 26332325
DOI: 10.1159/000439144 -
Veterinary Journal (London, England :... Oct 2021Kidney disease causes morbidity and mortality in dogs and cats. Serum creatinine concentration is an important surrogate marker for glomerular filtration rate (GFR)....
Kidney disease causes morbidity and mortality in dogs and cats. Serum creatinine concentration is an important surrogate marker for glomerular filtration rate (GFR). However, it is not always sensitive to small decreases in kidney function. Efforts to identify additional, more sensitive surrogate markers of GFR to improve detection of early kidney disease has led to the use of symmetrical dimethylarginine (SDMA) in veterinary medicine. There is insufficient information about the behavior of creatinine after an increase and the expected behavior of creatinine and SDMA in these cats and dogs. This study assesses the probability of persistence of increases in creatinine and the subsequent behavior of creatinine and SDMA in animals with persistently increased creatinine. For enrollment, three paired SDMA and creatinine concentrations were required: baseline (T0) with creatinine and SDMA at or below the upper reference limit (URL), T1, and T2 0.5-18 months after T1. The study included 4517 cats and 4576 dogs with increased T1 creatinine concentrations and 54,295 cats and 125,403 dogs with T1 creatinine at or below the URL. The probability of a persistently increased creatinine at T2 was approximately 58% for cats and 49% for dogs after a T1 increase. For animals without a T1 increase the probability of increased creatinine at T2 was only 7% for cats and 3% for dogs. For cats and dogs with persistently increased Cr, the probability of an increased SDMA concentration at T1 was 70-75%. By 24 months, that probability rose to 94% for cats and 88% for dogs.
Topics: Animals; Biomarkers; Cat Diseases; Cats; Creatinine; Dog Diseases; Dogs; Kidney; Longitudinal Studies; Renal Insufficiency, Chronic
PubMed: 34391919
DOI: 10.1016/j.tvjl.2021.105729