The impact of acute kidney injury with or without recovery on long-term kidney outcome in patients undergoing living liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is associated with an increased incidence of poor liver graft and renal outcomes in patients who have undergone liver transplantation (LT). To date, no comprehensive study has compared patients with and without post-LT AKI and analyzed patients who recovered from AKI versus those who did not. METHODS: Patients who received living LT between January 2003 and January 2019 were enrolled. We diagnosed and classified AKI patients based on AKI-KDIGO guidelines by increment of creatinine after surgery when compared with serum creatinine on the day of surgery. The recovered AKI subgroup included recipients whose estimated glomerular filtration rate (eGFR) recovered more than 90% of baseline eGFR within 90 days after surgery. The risk of chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2) was investigated. RESULTS: A total of 392 patients, 77.3% men and mean ± standard deviation age 54.1 ± 8.4 years, met the eligible criteria and were divided into two groups (AKI vs non-AKI) and 243 (62%) patients developed AKI within 7 days after surgery. Compared with the non-AKI group, the AKI group was associated with an adjusted hazard ratio of 1.55 (95% CI 1.12-2.14) for the risk of incident CKD. Among AKI patients, 160 (65.8%) patients recovered renal function and 83 (34.2%) patients did not. Compared with the non-AKI group, the AKI non-recovery group was associated with an adjusted hazard ratio of 2.87 (95% CI 1.95-4.21) for the risk of incident CKD, while the AKI recovery group had no significant difference in the adjusted risk of incident CKD. CONCLUSIONS: Post-LT AKI is associated with subsequent risk of CKD development. Taking into account recovery status, AKI was no longer associated with a higher risk of CKD if renal function recovered within 90 days after surgery. Identification and implementation of targeted and individualized therapies for patients at risk for AKI, particularly non-recovery AKI, is of paramount importance to reduce incident CKD during follow-up.

Association and risk factors of chronic kidney disease and incident diabetes: a nationwide population-based cohort study.

AIMS/HYPOTHESIS: Chronic kidney disease (CKD) is a known complication of diabetes mellitus, and insulin resistance is a well-known complication of CKD. However, there is no consensus in the published data on the association of CKD with incident diabetes. METHODS: A total of 15,403 people with CKD were identified from the Taiwan National Health Insurance Research Database to determine their risk of incident diabetes compared with that of 15,403 matched individuals without CKD. Fine and Gray regression models using death as a competing risk were performed to calculate adjusted HRs and 95% CIs. Risk factors for incident diabetes in people with CKD were also determined. RESULTS: The CKD cohort had a higher incidence rate of diabetes compared with the non-CKD cohort (11.23/1000 person-years vs 8.93/1000 person-years). In the fully adjusted model, CKD was a significant and independent predictor of incident diabetes (adjusted HR 1.204; 95% CI 1.11, 1.31). The influence of CKD on incident diabetes showed consistent results in three levels of sensitivity analysis. In the CKD cohort, the significant risk factors for incident diabetes included increased age, geographical location, hypertension, hyperlipidaemia and gout. Of these, hypertension was associated with the highest risk of developing incident diabetes (adjusted HR 1.682; 95% CI 1.47, 1.93). CONCLUSIONS/INTERPRETATION: People with CKD were at higher risk of developing incident diabetes. People with CKD and hypertension, hyperlipidaemia, increased age or gout and who lived in certain geographical regions of Taiwan were more likely to develop diabetes as a complication compared with people without those characteristics.

The role of uric acid in chronic kidney disease patients.

AIM: Chronic kidney disease (CKD) is always associated with hyperuricaemia. However, the studies evaluating the clinical implications of hyperuricaemia have shown conflicting results in these patients. METHODS: A retrospective observational study was conducted in 2408 stage 3-5 CKD patients. Instead of one baseline uric acid (UA) level, the averaged level of the two consecutive measurements for each participant was used as the predictor for the outcomes of the study, which included mortality, renal outcomes, and hospitalization risk. A multivariate Cox proportional hazards model and logistic regression model were performed to determine the independent risk factor. RESULTS: The mean UA level was 0.46 ± 0.106 mmol/L. Of the 2408 patients, there were 563 (23.3%) deaths, 143 (5.9%) cardiovascular deaths, 652 (27%) subjects commencing renal replacement therapy (RRT), 664 (27.5%) subjects with rapid renal progression, 1937 (58%) patients requiring hospitalization and 404 (16.7%) patients with CVD hospitalization during a mean follow-up of approximately 3.03 years. After multivariate adjustments, a 1-mg/dL increase in uric acid level was associated with a hazard ratio (HR) of 1.26 for RRT (P = 0.002), an odds ratio (OR) of 1.27 for rapid renal progression (P = 0.001), an HR of 1.19 for all-cause hospitalization (P < 0.001), and an HR of 1.12 for cardiovascular disease (CVD) hospitalization (P = 0.02), but not significantly with all-cause mortality and cardiovascular death at the end of follow-up. CONCLUSIONS: In stage 3-5 CKD patients, hyperuricaemia was associated with a higher risk of renal replacement therapy, rapid renal progression and hospitalization for all causes or CVD, but not with all-cause mortality or cardiovascular mortality.

U-shaped relationship between uric acid and residual renal function decline in continuous ambulatory peritoneal dialysis patients.

AIM: There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients. METHODS: A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria. RESULTS: The average rate of RRF decline was -0.12 ± 0.22 mL/min per month. Multivariate analysis showed that lower UA group (<0.372 mmol/L), higher UA group (≧0.421 mmol/L), male gender, diabetes mellitus (DM), the use of calcium channel blocker (CCB), and RRF at baseline were linked positively with the rate of RRF decline; on the other hand, independence in dialysate exchanges and BUN were negatively associated with the risk of RRF decline. In addition, male gender, DM, diuretics, and CCB were associated with a higher risk of progression to anuria, whereas 24-h urine amount at baseline conferred a protective role in the development of anuria. CONCLUSIONS: A U-shaped relationship was found between UA levels and the rate of RRF decline in patients on CAPD, with a faster decline rate in those of higher and lower UA groups.

Effects of stroke on changes in heart rate variability during hemodialysis.

BACKGROUND: Stroke and low heart rate variability (HRV) are both associated with an unfavorable prognosis in hemodialysis patients. The relationship between stroke and changes in HRV during hemodialysis remains unclear. METHODS: This study measured differences between predialysis and postdialysis HRV (△HRV) in 182 maintenance hemodialysis patients, including 30 patients with stroke, to assess changes in HRV during hemodialysis, and also to compare results to 114 healthy controls. RESULTS: All predialysis HRV measurements had no differences between stroke patients and those without stroke, but were lower than healthy controls. Postdialysis very low frequency (VLF) (P < 0.001), low frequency (LF) (P = 0.001), total power (TP) (P < 0.001) and the LF/high frequency (HF) ratio (P < 0.001) increased significantly relative to predialysis values in patients without stroke, whereas postdialysis HRV did not increase in stroke patients. After multivariate adjustment, dialysis vintage was negatively associated with △VLF (ß = -0.698, P = 0.046), △LF (ß = -0.931, P = 0.009), and △TP (ß = -0.887, P = 0.012) in patients without stroke. Serum intact parathyroid hormone (ß = -0.707, P = 0.019) was negatively associated with △LF. Total cholesterol (ß = -0.008, P = 0.001) and high sensitivity C-reactive protein (ß = -0.474, P = 0.012) were inversely correlated with the △LF/HF ratio in patients without stroke. CONCLUSION: HRV in hemodialysis patients is lower than in the general population. Increase in △HRV was observed in hemodialysis patients without stroke but not in stroke patients. This result suggests suppressed autonomic nervous reactions against volume unloading during hemodialysis, which might contribute to unfavorable outcomes in hemodialysis patients but even more so in those with prior stroke. Nephrologists should notice the importance of △HRV especially in high-risk patients.

Serum globulin is a novel predictor of mortality in patients undergoing peritoneal dialysis.

Serum globulin, which is composed mainly of immunoglobulins and acute phase proteins, can be considered as reflecting the inflammatory state. We conducted the present study to investigate the role of globulin in mortality risk in patients undergoing peritoneal dialysis (PD). The study participants were categorized by the median globulin value (2.8 g/dL) as the high globulin group (≥ 2.8 g/dL), and low globulin group (< 2.8 g/dL). Serum globulin is calculated by the equation: (serum total protein-serum albumin). The area under the curve (AUC) by the receiver operating characteristics curve analysis was calculated to compare the mortality prediction capacity of globulin with that of ferritin, and WBC counts. Among the 554 patients, 265 (47.83%) were men, the mean age was 52.91 ± 15.54 years and the body mass index was 23.44 ± 3.88 kg/m2. Multivariate Cox models showed the high globulin group had higher mortality risks of all-cause and cardiovascular disease (CVD), compared with the low globulin group with adjusted HRs of 2.06 (95% CI 1.39-3.05) and 1.94 (95% CI 1.18-3.16), respectively. The AUC of univariate and multivariate models for all-cause mortality resulted in higher AUC values for globulin than for ferritin and white blood cell (WBC) counts. In patients undergoing PD, the serum globulin can serve as a novel and independent determinant of predicting overall and CVD- associated mortality.

Anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary hemorrhage in the course of pulmonary tuberculosis.

A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

Association of Albumin and Globulin with Mortality Risk in Incident Peritoneal Dialysis Patients.

Background: Nutrition and inflammation have been implicated in predicting mortality in patients on peritoneal dialysis (PD). Serum albumin and globulin can be regarded for the nutritional and inflammatory status. However, there is lack of data to evaluate the synergistic effect of albumin and globulin on mortality prediction. Methods: In 554 patients initiating PD from January 2001 to July 2016, we divided them into four groups by the combination of two categories of low vs. high albumin and low vs. high globulin. The median values for albumin and globulin were chosen to classify them into low or high groups. Their associations with all-cause and cardiovascular (CV) mortality were examined in Cox regression models adjusted for confounding clinical and laboratory data. Results: Patients, 52.91 ± 15.2 years old and 47.8% men, had a median (interquartile range) value of 3.3 (2.9−3.8) g/dL for albumin and 2.8 (2.5−3.2) g/dL for globulin, respectively. Patients with low albumin and high globulin had the highest all-cause mortality and CV mortality, with adjusted hazard ratios of 3.87 (95% CI 1.83−8.20, p < 0.001) and 5.65 (95% CI 2.23−14.34, p < 0.001), respectively, compared with those with a high albumin and low globulin having the lowest mortality rate. Sensitivity analyses further confirmed this relationship. Conclusions: A patient profile of either low albumin or high globulin is linked to a higher risk for mortality, particularly for a profile of both low albumin and high globulin compared with one without either of them. Further studies are needed to explore the mechanisms underlying this phenomenon and how to improve clinical outcomes in those high-risk patients.

Infection in Living Donor Liver Transplantation Leads to Increased Risk of Adverse Renal Outcomes.

(1) Background: Little is known about the subsequent renal function change following incident infectious diseases in living-donor liver transplant (LT) recipients. (2) Methods: We studied patients who underwent living-donor LT from January 2003 to January 2019 to evaluate the association of incident hospitalization with major infections or pneumonia with adverse renal outcomes, including a sustained 40% reduction in estimated glomerular filtration rate (eGFR) and renal composite outcome (a 40% decline in eGFR, end-stage renal disease, or death.). Multivariable-adjusted time-dependent Cox models with infection as a time-varying exposure were used to estimate hazard ratio (HR) with 95% confidence interval (CI) for study outcomes. (3) Results: We identified 435 patients (mean age 54.6 ± 8.4 years and 76.3% men), of whom 102 had hospitalization with major infections during follow-up; the most common cause of infection was pneumonia (38.2%). In multiple Cox models, hospitalization with a major infection was associated with an increased risk of eGFR decline > 40% (HR, 3.32; 95% CI 2.13−5.16) and renal composite outcome (HR, 3.41; 95% CI 2.40−5.24). Likewise, pneumonia was also associated with an increased risk of eGFR decline > 40% (HR, 2.47; 95% CI 1.10−5.56) and renal composite outcome (HR, 4.37; 95% CI 2.39−8.02). (4) Conclusions: Our results illustrated the impact of a single infection episode on the future risk of adverse renal events in LT recipients. Whether preventive and prophylactic care bundles against infection and judicious modification of the immunosuppressive regimen benefit renal outcomes may deserve further study.

Association of Hematuria with Renal Progression and Survival in Patients Who Underwent Living Donor Liver Transplant.

BACKGROUND: This study aimed to determine the association between episodic or persistent hematuria after liver transplantation and long-term renal outcomes. METHODS: Patients who underwent living donor liver transplantation between July 2005 and June 2019 were recruited and divided into two groups based on the finding of microscopic or gross hematuria after transplantation. All patients were followed up from the index date until the end date in May 2020. The risks of chronic kidney disease, death, and 30% and 50% declines in estimated glomerular filtration rate (eGFR) were compared between groups. RESULTS: A total of 295 patients underwent urinalysis for various reasons after undergoing transplantation. Hematuria was detected in 100 patients (group A) but was not present in 195 patients (group B). Compared with group B, group A had a higher risk of renal progression, including eGFR decline >50% [aHR = 3.447 (95%CI: 2.24~5.30), p < 0.001] and worse survival. In addition, patients who took non-steroidal anti-inflammatory drugs (NSAIDs) continuously for over seven days within six months before transplant surgery had high risks of rapid renal progression, including a >30% decline in eGFR [aHR = 1.572 (95%CI: 1.12~2.21), p = 0.009)]. CONCLUSION: Development of hematuria after surgery in patients who underwent living donor liver transplant and were exposed to NSAIDs before surgery were associated with worse long-term renal dysfunction and survival.

Comparison of typical endocapillary and atypical mesangial proliferation in postinfectious glomerulonephritis.

BACKGROUND: There is a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis (PIGN). We conducted this retrospective study to compare the clinicopathological features between two distinct morphology of PIGN. METHODS: Thirteen patients with typical endocapillary proliferation and eight patients with atypical mesangial proliferation were enrolled in this study. The patients' records were reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. RESULTS: In comparison of histological parameters, glomerular neutrophil infiltration was more commonly present in typical endocapillary proliferation group (p = 0.018). Glomerular IgA dominant or co-dominant deposition was more frequently seen in atypical mesangial proliferation group (p = 0.032). In a comparison of clinical parameters, atypical mesangial proliferation group had lesser degrees of proteinuria, higher serum levels of complement, and higher rates of staphylococcal infection, although none of the differences was statistically significant. Glomerular morphology did not seem to affect the renal outcome. Moreover, our data suggested that the percentage of patients with atypical mesangial proliferation significantly increased over time (p < 0.001). CONCLUSIONS: Atypical mesangial proliferation may represent a resolution stage of PIGN. The nature of subclinical infection with a more protracted course may contribute to the increasing recognition of this resolving PIGN at the time of renal biopsy. Another possible explanation is that the atypical morphology may be a peculiar pattern of post-staphylococcal glomerulonephritis, which was increasingly identified in PIGN over the past 10 years.

The CHA2DS2-VASc score predicts chronic kidney disease among patients with atrial fibrillation.

BACKGROUND: It is unclear how the CHA2DS2-VASc score can predict subsequent chronic kidney disease (CKD) and end-stage renal disease (ESRD) among atrial fibrillation (AF) patients. METHODS: We identified incident AF patients without CKD between 2000 and 2013 from the National Health Insurance Research Database (NHIRD) of Taiwan and calculated the CHA2DS2-VASc score for each patient. Adjusted hazard ratio (HR) with 95% confidence interval (CI) was estimated from multivariate cause-specific Cox models to assess the risk of CKD and ESRD associated with the CHA2DS2-VASc score. RESULTS: A total of 8764 participants with AF who did not have CKD were included in the analysis. The mean age was 69.63 ± 13.48 years and 4800 (54.8%) were males. The adjusted HR of CKD displayed a stepwise increase with the increase in the CHA2DS2-VASc score. When compared with those with a CHA2DS2-VASc score of 0, the adjusted HRs of CKD were 1.57 (95% CI 1.09-2.26), 2.04 (95% CI 1.42-2.94), 2.48 (95% CI 1.70-3.62), 2.88 (95% CI 1.95-4.26), 3.29 (95% CI 2.18-4.95) and 4.00 (95% CI 2.61-6.13) for the AF patients with a CHA2DS2-VASc score of 1, 2, 3, 4, 5 and ≥ 6, respectively. Similarly, as the CHA2DS2-VASc score increased, the adjusted HR of ESRD showed a gradual increase. CONCLUSIONS: Patients with a higher CHA2DS2-VASc score were linked to a higher risk of CKD and ESRD in a dose-dependent effect, i.e. the incidence of CKD/ESRD increased with the increasing CHA2DS2-VASc score.

Superiority of albumin-globulin ratio over albumin to predict mortality in patients undergoing peritoneal dialysis.

There is increasing evidence showing that albumin-globulin ratio (AGR) can predict the survival of patients in many types of malignancies. However, no study was done to explore the value of AGR in peritoneal dialysis (PD) patients. A total of 554 incident patients undergoing PD from January 2001 through July 2016 were enrolled for this retrospective observational study. The outcomes of interest were all-cause mortality and cardiovascular disease (CVD) mortality. Baseline patient's socio-demographic data, pharmacotherapy, comorbidities, laboratory and PD-related parameters were collected and used in the multivariate Cox models. The predictive value of AGR on mortality risk was compared with other markers using area under the receiver operating characteristic curve (AUC) analysis. Among the study participants, there were 265 (47.83%) men and the mean follow-up time was 3.87 ± 3.15 years. Univariate Cox analysis showed that low AGR was significantly associated with worse outcomes in terms of all-cause and CVD mortality and it remained an independent predictor in the multivariate models. The fully adjusted hazard ratios for the low AGR group versus high AGR group were 2.12 (95% CI 1.34-3.35, p = 0.001) and 2.58 (95% CI 1.42-4.7, p = 0.002) for all-cause and CVD mortality, respectively. The predictive ability of AGR for mortality risk was superior to that of other biomarkers based on AUC calculations. In conclusion, low AGR was independently associated with higher all-cause and CVD mortality risks in patients undergoing PD.

Synergistic Anticancer Effects of Gemcitabine with Pitavastatin on Pancreatic Cancer Cell Line MIA PaCa-2 in vitro and in vivo.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an overall 5-year survival rate of 9.3%, and this malignancy is expected to become the second leading cause of cancer-related death by 2030. Gemcitabine resistance develops within weeks of PDAC patient's chemotherapeutic initiation. Statins, including pitavastatin, have been indicated to have anticancer effects in numerous human cancer cell lines. Thus, in this study, we hypothesized that a combination of gemcitabine and pitavastatin may have a greater anticancer effect than gemcitabine alone on the human pancreatic carcinoma cell line MIA PaCa-2. METHODS: The anticancer effects of gemcitabine with pitavastatin were evaluated using human MIA PaCa-2 cell line in vitro and in vivo Balb/c murine xenograft tumor model. Cell viability was assessed with CCK-8, and cell migration was stained by crystal violet. Cell cycle distribution, apoptosis and mitochondrial membrane potential were examined by flow cytometry. Activation of drug transporters (hENTs, hCNTs), intracellular drug activating (dCK) and inhibition of inactivating enzymes (RRMs) pathways were assessed by Western blotting analysis. Molecular mechanisms and signaling pathways of apoptosis, necrosis and autophagy also were assessed by Western blotting. RESULTS: We observed that gemcitabine and pitavastatin synergistically suppressed the proliferation of MIA PaCa-2 cells through causing sub-G1 and S phase cell cycle arrest. Activation of apoptosis/necrosis was confirmed by annexin V/propidium iodide double staining, which showed increasing levels of active caspase 3, cleaved poly(ADP-ribose) polymerase and the RIP1-RIP3-MLKL complex. Moreover, gemcitabine-pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. Furthermore, this combination improved drug cellular metabolism pathway, mitochondria function and activated autophagy as part of the cell death mechanism. In vivo, gemcitabine-pitavastatin effectively inhibited tumor growth in a nude mouse mode of Mia PaCa-2 xenografts without observed adverse effect. CONCLUSION: Combined gemcitabine-pitavastatin may be an effective novel treatment option for pancreatic cancer.

Association between Albumin-Globulin Ratio and Mortality in Patients with Chronic Kidney Disease.

BACKGROUND: Malnutrition and inflammation are highly prevalent and tightly regulated with each other in chronic kidney disease (CKD) patients. Inflammation can lead to malnutrition in patients with sufficient nourishment, while malnutrition may also induce an inflammatory response. This study investigated whether the albumin-globulin ratio (AGR) can predict the mortality risk in CKD patients. METHODS: We enrolled 956 stage 3-5 CKD patients retrospectively at a medical center. Patients' baseline characteristics including demographics, laboratory data, pharmacotherapy, and comorbidities were collected for statistical adjustments. The study patients were stratified into three AGR groups according to similar magnitudes of hazards for mortality as follows: low AGR group, AGR ≤ 1.0; moderate AGR group, 1.1 ≤ AGR < 1.3; high AGR group, AGR ≥1.3. Multivariate Cox proportional hazard analysis was performed to evaluate the association of the AGR with the study outcomes, including overall and cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 2.44 years, 108 (11.3%) deaths were recorded and 50 patients died from CVD. In adjusted model 1, the moderate AGR group was associated with hazard ratios (HR) of 0.57 (95% CI = 0.36-0.90, p = 0.016) and 0.52 (95% CI = 0.28-0.98, p = 0.043) for all-cause and CVD mortality compared with the low AGR group, respectively. The high AGR group was associated with HRs of 0.49 (95% CI = 0.27-0.90, p = 0.021) and 0.27 (95% CI = 0.1-0.74, p = 0.01) for all-cause and CVD mortality compared with the low AGR group, respectively. Similar results were obtained in the adjusted model 2 (inverse probability of the group weighted Cox model). In addition, the association between the AGR and mortality risk remained significant when the AGR was treated as a continuous variable. CONCLUSION: AGR is a significant biomarker predicting overall and cardiovascular mortality risk independent of various important factors amongst stage 3-5 CKD patients. We suggest that the AGR may be a simple and inexpensive measurement for detecting CKD patients at risk of mortality.

Effects of Prevalent and Incident Chronic Kidney Disease on Cardiovascular Events in Patients with Atrial Fibrillation.

BACKGROUND: Chronic kidney disease (CKD) is a well-known complication of atrial fibrillation (AF) but how the incident CKD affects the clinical outcomes amongst AF patients is not clear. METHODS: Our study data were retrieved from National Health Insurance Research Data for the period from 1996 to 2013. Incident AF patients were classified as non-CKD group (n = 7272), prevalent CKD group (n = 2104), and incident CKD group (n = 1507) based on administrative codes. Patients with prevalent CKD were those participants who already had CKD ahead of the index date of AF, whereas patients with incident CKD were those who developed CKD after the index date and the remaining patients were designated as non-CKD. Multivariate-adjusted time-dependent Cox models were conducted to estimate the associations of CKD status with the outcomes of interest, including heart failure (HF), acute myocardial infarction (AMI), stroke or systemic thromboembolism, all-cause mortality, and cardiovascular (CV) mortality, expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The mean age was 70.8 ± 13.3 years, and 55.4% of the studied population were men. In Cox models, the adjusted rate of HF, AMI, all-cause mortality, and CV mortality was greater in the prevalent and incident CKD groups, ranging from 1.31-fold to 4.28-fold, compared with non-CKD group. Notably, incident CKD was associated with higher rates of HF (HR, 1.8; 95% CI, 1.67-1.93), stroke or systemic thromboembolism (HR, 1.33; 95% CI, 1.22-1.45), AMI (HR, 1.46; 95% CI, 1.25-1.71), all-cause mortality (HR, 1.76; 95% CI, 1.68-1.85), and CV mortality (HR, 2.13; 95% CI, 1.92-2.36) compared with prevalent CKD. CONCLUSION: The presence of CKD was associated with higher risks of subsequent adverse clinical outcomes in patients with AF. Our study was even highlighted by the finding that incident CKD was linked to higher risks of outcome events compared with prevalent CKD.

Effects of Prevalent and Incident Atrial Fibrillation on Renal Outcome, Cardiovascular Events, and Mortality in Patients with Chronic Kidney Disease.

BACKGROUND: Little is known about how incident atrial fibrillation (AF) affects the clinical outcomes in chronic kidney disease (CKD) patients and whether there is a different influence between pre-existing and incident AF. METHODS: Incident CKD patients from 2000 to 2013 were retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan and they were classified as non-AF (n = 15,251), prevalent AF (n = 612), and incident AF (n = 588). The outcomes of interest were end-stage renal disease (ESRD) requiring dialysis, all-cause mortality, cardiovascular (CV) mortality, acute myocardial infarction (AMI), stroke or systemic thromboembolism. RESULTS: Compared with CKD patients without AF, those with prevalent or incident AF were associated with higher adjusted rates of ESRD (hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.32-1.48; HR, 2.91; 95% CI, 2.74-3.09, respectively), stroke or systemic thromboembolism (HR, 1.89; 95% CI, 1.77-2.03; HR, 1.67; 95% CI, 1.54-1.81, respectively), AMI (HR, 1.24; 95% CI, 1.09-1.41; HR, 1.99; 95% CI, 1.75-2.27, respectively), all-cause mortality (HR, 1.64; 95% CI, 1.56-1.72; HR, 2.17; 95% CI, 2.06-2.29, respectively), and CV mortality (HR, 2.95; 95% CI, 2.62-3.32; HR, 4.61; 95% CI, 4.09-5.20, respectively). Intriguingly, CKD patients with prevalent AF were associated with lower adjusted rates of ESRD, AMI, all-cause mortality, and CV mortality compared with those with incident AF. CONCLUSION: Both incident and prevalent AF were independently associated with greater risks of AMI, all-cause mortality, CV mortality, ESRD, and stroke or systemic thromboembolism. Our findings are novel in that, compared with prevalent AF, incident AF possessed an even higher risk of some clinical consequences, including ESRD, all-cause mortality, CV mortality, and AMI.

An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis.

Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24⁻0.68, p = 0.001), 0.4 (95% CI 0.2⁻0.81, p = 0.01), and 0.47 (95% CI 0.19⁻1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69⁻0.9, p = 0.07), 0.79 (95% CI, 0.61⁻1.01, p = 0.06), and 0.79 (95% CI, 0.48⁻1.21, p = 0.32) for men and 0.57 (95% CI, 0.44⁻0.73, p < 0.001), 0.6 (95% CI, 0.41⁻0.87, p = 0.006), and 0.41 (95% CI, 0.26⁻0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis.

Effect of New-Onset Diabetes Mellitus on Renal Outcomes and Mortality in Patients with Chronic Kidney Disease.

BACKGROUND: The incidence rates of diabetes mellitus (DM) and chronic kidney disease (CKD) are increasing worldwide and their coexistence can have a large negative impact on clinical outcomes. However, it is unclear how incident DM affects CKD patients. METHODS: Incident CKD patients between 2000 and 2013 were identified from the National Health Insurance Research Database of Taiwan; they were classified as non-DM (n = 10,356), pre-existing DM (n = 6982), and incident DM (n = 1103). Non-DM cases were patients who did not develop DM before the end of the observation period. The outcomes of interest were end-stage renal disease (ESRD), mortality, and composite outcome (ESRD or death). The association between the DM groups and clinical outcomes was estimated using the inverse probability of group-weighted (IPW) multivariate-adjusted time-dependent Cox regression models. RESULTS: During the study period of 14 years, 1735 (16.6%) patients in the non-DM group reached ESRD compared with 2168 (31.05%) in the pre-existing DM group and 111 (11.03%) in the incident DM group (p < 0.001). Moreover, 2219 (21.43%) patients in the non-DM group died compared with 1895 (27.14%) in the pre-existing DM group and 303 (27.47%) in the incident DM group (p < 0.001). Compared with the non-DM group, the pre-existing DM group was associated with a higher risk of ESRD [hazard ratio (HR) 2.54; 95% confidence interval (CI 2.43⁻2.65), death (HR 2.23; 95% CI 2.14⁻2.33), and a composite outcome (HR 2.29; 95% CI 2.21⁻2.36). Similarly, incident DM was also associated with a higher risk of ESRD (HR 1.12; 95% CI 1.06⁻1.19), death (HR 2.48; 95% CI 2.37⁻2.60), and a composite outcome (HR 1.77; 95% CI 1.70⁻1.84) compared with the non-DM group. Factors contributing to incident DM included old age, low monthly income, and having hypertension, hyperlipidemia, and ischemic heart disease, while pentoxifylline reduced the risk of incident DM. CONCLUSION: Similarly to pre-existing DM, CKD patients with incident DM carried a higher risk of ESRD, mortality, and a composite outcome compared with those with non-DM. For those at risk of incident DM, strict monitoring and intervention strategies must be adopted to help improve their clinical outcomes.

Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease.

BACKGROUND: Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain unclear. METHODS: We identified predialysis stage 3⁻4 chronic kidney disease (CKD) patients between 2000 and 2013 from the Longitudinal Health Insurance Database 2005 (LHID 2005). The outcomes of interest were end-stage renal disease (ESRD), major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), hyperkalemia-associated hospitalization (HKAH), all-cause mortality and cardiovascular mortality. The Fine and Gray sub-distribution hazards approach was adopted to adjust for the competing risk of death. RESULTS: After the propensity score matching, 693 patients with stage 3⁻4 CKD were spironolactone users and 1386 were nonusers. During the follow-up period, spironolactone users had a lower incidence rate for ESRD than spironolactone non-users (39.2 vs. 53.69 per 1000 person-years) and a higher incidence rate for HKAH (54.79 vs. 18.57 per 1000 person-years). The adjusted hazard ratios for ESRD of spironolactone users versus non-users were 0.66 (95% CI, 0.51⁻0.84; p value < 0.001) and 3.17 (95% CI, 2.41⁻4.17; p value < 0.001) for HKAH. A dose-response relationship was found between spironolactone use and risk of ESRD and HKAH. There were no statistical differences in MACE, HHF, all-cause mortality and cardiovascular mortality between spironolactone users and non-users. CONCLUSION: Spironolactone represented a promising treatment option to retard CKD progression to ESRD amongst stage 3⁻4 CKD patients, but strategic treatments to prevent hyperkalemia should be enforced.