Factors associated with survival in dogs with chronic kidney disease

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Abstract

Background: Chronic kidney disease (CKD) is associated with morbidity and mortality in dogs. Plasma fibroblast growth factor‐23 (FGF‐23) concentration is an independent predictor of CKD progression and survival in cats and people with CKD. Objectives: To investigate the relationship among FGF‐23, parathyroid hormone (PTH), vitamin D metabolites, and other clinical variables with survival time in dogs with CKD. Animals: Twenty‐seven azotemic CKD dogs. Methods: Dogs were recruited prospectively into the study and followed until death or study conclusion. Dogs were International Renal Interest Society (IRIS) staged into stage 2 (n = 9), stage 3 (n = 12), and stage 4 (n = 6) CKD. Survival times were calculated from the date of study inclusion. Univariable Cox regression was used to assess variables associated with survival including body condition score (BCS), muscle condition score, hematocrit, creatinine, CKD stage, serum phosphorus, urine protein:creatinine ratio (UPC), calcium phosphorus product (CaPP), PTH, 25‐hydroxyvitamin D, 1,25‐‐dihydroxyvitamin D, and FGF‐23 concentrations. Results: Significant hazard ratios (hazard ratio; 95% confidence interval; P value) were as follows: BCS < 4/9 (1.579; 1.003‐2.282; P = .05), muscle atrophy (2.334; 1.352‐4.030; P = .01), increased creatinine (1.383; 1.16‐1.64; .01), hyperphosphatemia (3.20; 1.357‐7.548; P = .005), increased UPC (3.191; 1.310‐7.773; P = .01), increased CaPP (4.092; 1.771‐9.454; P = .003), and increased FGF‐23 (2.609; 1.090‐6.240; P = .05). Survival times for each IRIS CKD stage were significantly different (P = .01). Conclusions and Clinical Importance: Multiple variables, including FGF‐23, were associated with duration of survival in CKD dogs. FGF‐23 could be a prognostic marker in dogs with CKD.

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Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease.

Tamara Isakova, Huiliang Xie, Wei Yang … (2011)

A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease. To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease. A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008. All-cause mortality and end-stage renal disease. At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2). Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.

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Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities.

Edmund G Lowrie, Nancy Lew (1990)

Logistic regression analysis was applied to a sample of more than 12,000 hemodialysis patients to evaluate the association of various patient descriptors, treatment time (hours/treatment), and various laboratory tests with the probability of death. Advancing age, white race, and diabetes were all associated with a significantly increased risk of death. Short dialysis times were also associated with high death risk before adjustment for the value of laboratory tests. Of the laboratory variables, low serum albumin less than 40 g/L (less than 4.0 g/dL) was most highly associated with death probability. About two thirds of patients had low albumin. These findings suggest that inadequate nutrition may be an important contributing factor to the mortality suffered by hemodialysis patients. The relative risk profiles for other laboratory tests are presented. Among these, low serum creatinine, not high, was associated with high death risk. Both serum albumin concentration and creatinine were directly correlated with treatment time so that high values for both substances were associated with long treatment times. The data suggest that physicians may select patients with high creatinine for more intense dialysis exposure and patients with low creatinine for less intense treatment. In a separate analysis, observed death rates were compared with rates expected on the basis of case mix for these 237 facilities. The data suggest substantial volatility of observed/expected ratios when facility size is small. Nonetheless, a minority of facilities (less than or equal to 2%) may have higher rates than expected when compared with the pool of all patients in this sample. The effect of various laboratory variables on mortality is substantial, while relatively few facilities have observed death rates that exceed their expected values. Therefore, we suggest that strategies designed to improve the overall mortality statistic for dialysis patients in the United States would be better directed toward improving the quality of care for all patients, particularly high-risk patients, within their usual treatment settings rather than trying to identify facilities with high death rate for possible regulatory intervention.

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FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.

Randal Kaufman, Tom Greene, Michel Chonchol … (2011)

Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73 m(2). During a median follow-up of 2.9 yr, 453 (41%) patients died from any cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progressively higher risk for death, adjusted for confounders (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08] for the second through fourth quartiles, respectively). In addition, compared with the lowest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated risk for cardiovascular events and initiation of chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-cause mortality, cardiovascular events, and initiation of chronic dialysis.