Differences in characteristics and risk factors for acute kidney injury between elderly and very elderly patients: a retrospective review.

BACKGROUND: Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study aimed to clarify the characteristics and risk factors for AKI in this population. METHODS: This retrospective observational study was performed with the clinical data of all outpatients and inpatients aged ≥ 65 years at the time of enrolment at Kochi Medical School Hospital between 1 January 1981 and 31 December 2021. The primary cohort was divided into those aged 65-74 and ≥ 75 years. The primary outcome was the occurrence of AKI. RESULTS: Of 83,822 patients, 38,333 were included in the 65-74-year-old group, whereas 45,489 were included in the ≥ 75-year-old group. Prevalences of the first AKI event in the 65-74-year-old and ≥ 75-year-old groups were 11.9% and 12.4%, respectively. Overall, lower estimated glomerular filtration rate, lower albumin level, lower or higher level of serum uric acid, and histories of diabetes mellitus, chronic heart failure, ischaemic heart disease, non-ischaemic heart disease, cerebrovascular disease, cancer, and liver disease were independent risk factors for an AKI event. The risk factors for AKI unique to each cohort were using non-steroidal anti-inflammatory drugs (NSAIDs) and loop diuretics (L-DI), and histories of hypertension (HT) and vascular diseases (VD) in men aged 65-74 years; using NSAIDs, angiotensin-converting enzyme inhibitors (ACEIs), L-DI and other diuretics (O-DI), and histories of HT and VD in men aged ≥ 75 years; using NSAIDs and O-DI and not using angiotensin-receptor blockers (ARBs), and a history of HT in women aged 65-74 years; and use of L-DI and a history of VD in women aged ≥ 75 years. Presence of proteinuria was a risk factor for developing AKI. CONCLUSIONS: Many AKI risk factors reported thus far are associated with AKI development. However, there are differences in the effects of the renin-angiotensin system inhibitors, ACEIs, and ARBs (ARBs may be protective). Additionally, the U-shaped relationship between AKI onset and uric acid levels differs between sexes in the elderly population, similar to other age groups, but this sex difference disappears in the very elderly population. Pre-existing chronic kidney disease is a risk factor for the development of AKI.

Incidence of acute kidney injury and decreased estimated glomerular filtration rate according to the site of cancer.

BACKGROUND: The epidemiology of renal impairment in patients with cancer remains unclear. We aimed to clarify associations between various cancer sites and renal impairment. METHODS: We reviewed data from 5674 patients aged ≥ 18 years receiving cancer treatment at a single hospital facility. The primary endpoints were the occurrence of acute kidney injury (AKI), a 30% decrease in the estimated glomerular filtration rate (eGFR), or death. Survival time was defined as the time from study enrolment to AKI occurrence. Kaplan-Meier and Cox proportional hazard analyses were performed. RESULTS: Hazard ratios (HRs) for AKI occurrence and a ≥ 30% decline in eGFR were significantly higher for kidney, urinary tract, pancreatic, liver, and gallbladder cancers than for colon cancer. Compared with colon cancer, digestive tract cancer showed a significantly higher HR for AKI occurrence alone. The HRs for a ≥ 30% decline in eGFR were significantly higher for patients aged 71‒77 years or ≥ 78 years than for those aged < 68 years, and for patients with eGFR ≥ 90 mL/min/1.73 m2 or 30-44 mL/min/1.73 m2 than for those with eGFR = 45‒59 mL/min/1.73 m2. CONCLUSIONS: Kidney, urinary, hepatobiliary, or pancreatic cancer are associated with a higher risk of AKI development and eGFR decrease than other cancers. Renal function changes should be more closely monitored in patients with these cancers.

Identification of risk factors associated with oral 5-aminolevulinic acid-induced hypotension in photodynamic diagnosis for non-muscle invasive bladder cancer: a multicenter retrospective study.

BACKGROUND: To investigate risk factors for orally administered 5-aminolevulinic acid (ALA)-induced hypotension for bladder cancer patients receiving photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT). METHODS: Patients were categorized into two groups intraoperatively: a hypotensive group (minimum systolic blood pressure (SBP) ≤80 mmHg) and a non-hypotensive group (minimum SBP > 80 mmHg). We examined differences between the hypotensive group and non-hypotensive groups to identify clinical risk of ALA-induced hypotension using multivariate logistic regression analysis and decision tree analysis. RESULTS: Among 282 cases with ALA-PDD-assisted TURBT from three institutions who were screened, 245 patients were included in the final analysis. In total, 156 patients (63.7%) showed any grade of hypotension during ALA-PDD-assisted TURBT. General anesthesia and spinal anesthesia were induced intraoperatively in 113 patients (46.1%) and 132 patients (53.9%), respectively. Median SBP at baseline (before taking ALA) and at the beginning of anesthesia was 127 mmHg (range, 69-186 mmHg) and 124 mmHg (range, 69-186 mmHg), respectively. Median minimum SBP during ALA-PDD-assisted TURBT was 75 mmHg (range, 43-140 mmHg). Multivariate logistic regression analysis revealed that history of hypertension (odds ratio (OR) 7.568, p < 0.05) and general anesthesia (OR 14.435, p < 0.05) as significantly associated with an increased risk of hypotension incidence. Use of calcium antagonist showed significant negative associations with hypotension (OR 0.183, p < 0.05). Decision tree analysis showed presence of general anesthesia, age ≥ 74 years and American Society of Anesthesiologists physical status (ASA-PS) ≥2 as the most important discriminators. CONCLUSIONS: General anesthesia and hypertension were independent risk factors related to ALA-induced hypotension. In contrast, use of calcium antagonists was identified as a factor associated with reduced risk of ALA-induced hypotension.

Long-term continuous use of proton-pump inhibitors is associated with renal function decline in patients without acute kidney injury.

BACKGROUND: Proton-pump inhibitors (PPIs) are widely used to treat gastroesophageal reflex disease, peptic ulcer disease, and stress ulcer prophylaxis. This study estimated the progress rate of renal dysfunction in patients taking PPIs in clinical settings and compared the results with those of patients taking histamine-2 receptor antagonists (H2RAs). METHODS: We retrospectively reviewed patients' data collected from Kochi Medical School Hospital's information system between 2001 and 2019. Patients were classified into PPI and H2RA groups, and survival time was defined as the period between initial drug administration and a 30% decrease in estimated glomerular filtration rate (eGFR). RESULTS: On survival analysis, the PPI group was associated with higher event incidence rates compared to that in the H2RA group. The rate of underlying disease was significantly higher in the PPI group than in the H2RA group, with no significant differences in age and sex between the groups. Comparing the PPI group to the H2RA group, the use of aspirin, clopidogrel, statin, and angiotensin II receptor blocker was significantly higher, whereas the use of non-steroidal anti-inflammatory drugs and steroids was significantly less. Regarding survival rate and 30% decrease in eGFR, the PPI group had a significantly higher survival rate compared to that in the H2RA group at 730 days, but not earlier. PPI use, older age, and eGFR ≥ 90 mL/min/1.73 m2 exhibited high hazard ratios. CONCLUSIONS: PPI use was significantly associated with an increased risk of chronic kidney disease development compared to that with H2RA use.

Effects of transient acute kidney injury, persistent acute kidney injury and acute kidney disease on the long-term renal prognosis after an initial acute kidney injury event.

AIM: To clarify the effects of the duration of acute damage and/or loss of renal function following an acute kidney injury event on the renal prognosis after recovery. METHODS: We retrospectively reviewed data collected between 1995 and 2016 from the Kochi Medical School Hospital. Patients were stratified according to the time required for recovery with fluid therapy (expected to reflect the presence of renal dysfunction): ≤2 days after onset, transient injury group (n = 491); 3 to 7 days after onset, persistent injury group (n = 1076); and ≥ 8 days after onset, acute kidney disease group (n = 1046). The healthy group comprised 1000 randomly selected adult patients without acute kidney injury with at least two creatinine measurement results during the study. Survival time was defined as the time from recovery to a 30% decrease in the estimated glomerular filtration rate (primary endpoint). Kaplan-Meier and Cox proportional hazards analyses were conducted. RESULTS: Event incidence rates were higher for the transient injury, persistent injury and acute kidney disease groups than for the healthy group. Persistent injury and acute kidney disease presented a higher risk of renal function decline than transient injury following recovery. CONCLUSION: Transient acute kidney injury, persistent acute kidney injury and acute kidney disease resulted in functional decline and rapid chronic kidney disease progression risks despite recovery. Transient acute kidney injury recovery within 2 days could be associated with better long-term prognoses than persistent acute kidney injury and acute kidney disease persisting beyond 2 days.

Evaluation of the accuracy of estimated baseline serum creatinine for acute kidney injury diagnosis.

BACKGROUND: Modern epidemiologic studies of acute kidney injury (AKI) have been facilitated by the increasing availability of electronic medical records. However, pre-morbid reference serum creatinine (SCr) data are often unavailable in such records. Investigators substitute estimated baseline SCr with the eGFR 75 approach, instead of using actually measured baseline SCr. Here, we evaluated the accuracy of estimated baseline SCr for AKI diagnosis in the Japanese population. METHODS: Inpatients and outpatients aged 18-80 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using SCr levels. The non-AKI and AKI groups were selected using the following criteria: increase 1.5 times greater than baseline SCr ("baseline SCr") or increase 0.3 mg/dL greater than baseline SCr in 48 h ("increase in 48 h"). AKI accuracy defined by the estimated reference SCr, the average SCr value of the non-AKI population (eb-GFR-A approach), or the back-calculated SCr from fixed eGFR = 75 mL/min/1.73 m2 (eGFR 75 approach, or, eb-GFR-B approach in this study), was evaluated. RESULTS: We analyzed data from 131,358 Japanese patients. The number of patients with reference baseline SCr in the non-AKI and AKI patients were 29,834 and 8952, respectively. For AKI patients diagnosed using "baseline SCr", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 63.5 and 57.7%, respectively, while in AKI diagnosed using "increase in 48 h", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 78.7 and 75.1%, respectively. In non-AKI patients, false-positive rates of AKI misdiagnosed via eb-GFR-A and eb-GFR-B were 7.4 and 6.8%, respectively. CONCLUSIONS: AKI diagnosis using the average SCr value of the general population may yield more accurate results than diagnosis using the eGFR 75 approach when the reference SCr is unavailable.

Transition from acute kidney injury to chronic kidney disease: a single-centre cohort study.

BACKGROUND: The incidence of acute kidney injury (AKI) is increasing. AKI is currently recognised as an inducer of chronic kidney disease (CKD) and this is known as the 'AKI-CKD transition'. This study aimed to evaluate the rate of decline in estimated glomerular filtration rate (eGFR) associated with AKI events in individuals with and without pre-existing CKD. METHODS: Inpatients aged 18-80 years were retrospectively enrolled. AKI was diagnosed according to the kidney disease improving global outcomes (KDIGO) criteria using serum creatinine levels. Patients with a history of AKI events were divided into four groups according to eGFR before and after the AKI events. In each group, the eGFR levels after an AKI event were compared to those before the AKI event. Patients were further divided into eight groups according to clinical background based on underlying diseases, medications, and surgical history. RESULTS: We analysed data from 9651 patients with AKI. Not surprisingly, we found that eGFR levels during the first AKI event were significantly lower than levels before the event in each group. Furthermore, eGFR levels after the first AKI event were significantly lower than those before the first AKI event, and the eGFR levels after the second AKI event were significantly lower than those after the first AKI event. These trends were similar in each group irrespective of clinical background. CONCLUSIONS: Our study revealed that AKI events can cause a decline in kidney function and, as more AKI events occur, acceleration of this decline.

Effects of topiroxostat in hyperuricemic patients with chronic kidney disease.

BACKGROUND: Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD. METHODS: This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR. RESULTS: Topiroxostat treatment resulted in significant reduction in SUA (-1.53 mg/dL), systolic blood pressure (-8.9 mmHg), diastolic blood pressure (-5.0 mmHg), and urinary protein excretion (-795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly. CONCLUSIONS: Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.

Incidence of acute kidney injury among patients with chronic kidney disease: a single-center retrospective database analysis.

BACKGROUND: Acute kidney injury (AKI) is a serious complication among hospitalized individuals and is closely associated with chronic kidney disease (CKD). METHODS: This retrospective cohort study evaluated the incidences of AKI according to CKD stage at Kochi Medical School hospital during 1981-2011. AKI was defined and staged according to the kidney disease improving global outcomes criteria, using serum creatinine levels. RESULTS: We analyzed data from 122,653 Japanese patients (57,105 men, 46.6 %). The incidence of AKI was 7.8 % (95 % confidence interval 7.7-8.0 %). Compared to non-AKI patients, patients with stage 1-2 AKI were more likely to be men. Patients with stage 1-2 AKI were significantly older than non-AKI or stage 3 AKI patients. The incidences of AKI were 6.7, 5.9, 10.4, 18.4, 30.0, and 48.8 % among individuals with estimated glomerular filtration rates of ≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2, respectively; these were significantly different from the incidence for the baseline eGFR. The proportions of inpatients with AKI exhibited step-wise increases with more severe pre-existing reduced kidney function, and the proportions among outpatients exhibited step-wise increases with milder pre-existing reduced kidney function. CONCLUSIONS: CKD was a risk factor for AKI, and the incidence of AKI was positively associated with pre-existing reduced kidney function (CKD stage). We also found that the prevalence of AKI at early-stage CKD among outpatients was higher than expected. We suggest that outpatients should be monitored for AKI, given its unexpected incidence in that population.

Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital.

BACKGROUND AND OBJECTIVES: Recent studies have shown that both low and high levels of serum uric acid (SUA) before cardiovascular surgery are independent risk factors for postoperative acute kidney injury (AKI). However, these studies were limited by their small sample sizes. Here, we investigated the association between SUA levels and AKI by performing a retrospective database analysis of almost 30 years of data from 81,770 hospitalized patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENT: Hospitalized patients aged ≥18 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline (KDIGO) criteria. Multivariate logistic regression analyses were performed to investigate the independent association between SUA levels and the incidence of AKI. SUA levels were treated as categorical variables because the relationship between SUA and the incidence of AKI has been suggested to be J-shaped or U-shaped. In addition to stratified SUA levels, we considered kidney function and related comorbidities, medications, and procedures performed prior to AKI onset as possible confounding risk factors. RESULTS: The final study cohort included 59,219 adult patients. Adjusted odds ratios of AKI incidence were higher in both the high- and low-SUA strata. Odds ratios tended to become larger in the higher range of SUA levels in women than in men. Additionally, this study showed that AKI risk was elevated in patients with SUA levels ≤7 mg/dL. An SUA level >7 mg/dL is considered the point of initiation of uric acid crystallization. CONCLUSIONS: SUA level could be an independent risk factor for AKI development in hospitalized patients. Additionally, our results might suggest that intervention to lower SUA levels is necessary, even in cases of moderate elevation that does not warrant hyperuricemia treatment. Results also showed that SUA levels that require attention are lower for women than for men.

Effect of mild hyponatremia on in-hospital falls of elderly hospitalized patients: A retrospective, cohort study.

OBJECTIVES: This study investigated the association between hyponatremia and falls in elderly hospitalized patients, focusing on mild hyponatremia as a potential risk factor. MATERIALS AND METHODS: A retrospective analysis of 16,952 patients admitted to Kochi Medical School Hospital from 2012 to 2021 was performed. Serum sodium levels were categorized, and falls during a 30-day observation period were recorded. A Cox proportional hazards model and a machine learning model were used to estimate risk and explore interactions. RESULTS: Mild hyponatremia (130-134 mEq/L) was identified as an independent risk factor for falls (hazard ratio: 1.42, 95 % confidence interval 1.16-1.74), especially in patients with higher activities of daily living. The fall prediction model showed an area under the curve (AUC) of 0.780 (95 % confidence interval 0.751-0.806). CONCLUSION: A significant association between mild hyponatremia and falls in elderly hospitalized patients was found. The findings highlight the need for targeted fall prevention and further research into the underlying mechanisms. Mild hyponatremia may serve as a clinical marker for fall risk, especially in patients with independent activities of daily living.

[Improving data warehouse environments for efficient analysis of long time-series data].

Medical records contain enormous amounts of data. It is important to extract useful evidence from such data and feedback to clinical medicine. Evidence-based medicine (EBM) was introduced in the 1990s and has been widely used for more than 20 years, however, hospital information system environments that take advantage of the ideas of EBM have not yet been established. Recently, the numbers of medical institutions with multilateral search systems for the medical records stored in data warehouses (DWHs) have been increasing, but these institutions' systems cannot deal fully with issues such as data reliability and high-dimensional, high-speed searches. DWHs can control long time-series data. Although, the measurement methods and analytical equipment used have been modified and improved with advances in testing techniques, this may have induced shifting and/or fragmentation of these types of data. Furthermore, database design has to be flexible to satisfy the various demands of information retrieval; systems must therefore have the structures to deal with such demands. We report here our new system infrastructure, which exchanges data in order to absorb the data shifting associated with changes in the testing methods. The system enables the preparation of DWH environments that can be used to seamlessly analyze long time-series data, record in knowledge databases the results of comprehensive analyses of institutions' characteristics of laboratory diagnoses, and use the data in education, research and clinical practice.

Influence of hyperuricemia treatment on postoperative acute kidney injury among hyperuricemia patients: a single-center retrospective database analysis.

OBJECTIVE: Hyperuricemia has been reported to be associated with the development of postoperative acute kidney injury (pAKI). However, it remains underdetermined whether hyperuricemia treatment could decrease the potential risk of pAKI. Here, we investigated this hypothesis among hyperuricemia patients with previously normal renal function by performing a retrospective database analysis. RESULTS: The study screened 18,169 patients, and were examined preoperative serum creatinine, uric acid, and postoperative serum creatinine. Eight hundred thirty-six patients were finally analyzed for the study, of whom 232 were in the treatment group and 604 were in the non-treatment control group. After adjustment for multi-covariates including baseline (pre-treatment) serum uric acid (SUA) levels, the incidence of pAKI in the treatment group (9.05%; 95% CI 6.04-12.1%) was significantly lower than that in the control group (14.2%; 95% CI 11.2-17.2%). On the other hand, further adjusting for preoperative SUA levels, there was no significant difference in the expected incidence of pAKI between the groups.

Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder.

Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients.

Heavy alcohol intake is a risk factor for esophageal squamous cell carcinoma among middle-aged men: A case-control and simulation study.

Despite the advances in surgical techniques and treatments, the prognosis of esophageal cancer remains poor, since the disease is usually diagnosed at an advanced stage. Therefore, prevention plays an important role in reducing mortality. Smoking and alcohol intake are modifiable habits and are important risk factors for esophageal cancer. However, the number of large-scale studies that have investigated the association of the amount and duration of smoking and alcohol intake with esophageal cancer risk, while accounting for the effects of gender and cancer subtypes (squamous cell carcinoma and adenocarcinoma), is limited. Therefore, in this hospital-based matched case-control study we investigated this association while accounting for gender and subtype differences. Chinese male patients <60 years of age with esophageal squamous cell carcinoma (ESCC) from the Fourth Hospital of Hebei Medical University in China and healthy individuals were enrolled between January, 2002 and December, 2006. Each ESCC patient was age-matched to a control subject and a total of 535 pairs were enrolled in this study. The combined variables of amount and duration were created to elucidate their effect and association with ESCC. Multiple conditional logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) in this model, which included a family history of esophageal cancer, a combined smoking variable and a combined alcohol variable. A simulation study was subsequently performed to confirm the reliability of the results. The results of the present study demonstrated that a family history of esophageal cancer and the combined alcohol variable were significantly associated with ESCC risk. Heavy alcohol consumption and intake for ≤20 years increased the risk compared with no intake (OR=1.91, 95% CI: 1.25-2.92). Heavy alcohol consumption and intake for >20 years exhibited an even higher risk (OR=7.25, 95% CI: 3.12-16.83). These results were similar to those of the simulation. Heavy alcohol intake, even for a short duration, is a critical risk factor and may lead to the development of ESCC in Chinese males.