Temporal evolution of C-reactive protein levels and its association with the incident hospitalization risk among individuals with stage 3-4 chronic kidney disease.

BACKGROUND: Elevated C-reactive protein (CRP) levels as an inflammatory marker have been associated with poor outcomes in patients with chronic kidney disease (CKD). However, its single assessment may not reflect clinical significance before an adverse clinical endpoint. We studied the CRP level trajectories, which may be related with the intensity of the inflammatory process, and its association with time-to-first hospitalization in CKD. METHODS: A cohort of 739 patients with stage 3-4 CKD were retrospectively observed for seven years. The time-to-event outcome was all-cause hospitalization. Clinical and laboratory features were measured at baseline. Longitudinal changes in naturally logged CRP levels were modeled using the Joint Longitudinal-Survival model adjusted with baseline covariates. RESULTS: Logged CRP changes were evaluated with a median measurement (interquartile range) of 4 (2, 7), during a median (interquartile range) follow-up of 2.3 (1.2, 3.9) years. The estimated mean increase in logged CRP was 0.35 mg/L per year. 299 (40.5%) patients reached the endpoint, and increase in logged CRP with time was associated with increased risk of hospitalization (HR 1.96; 95% CI 1.05-3.66; p = 0.034), but baseline logged CRP did not have a significant effect on the time-to-first hospitalization (HR 0.98; 95% CI 0.85-1.13; p = 0.736). CONCLUSION: All-cause hospitalization was associated significantly with CRP trajectories. Temporal evolutions of these repeatedly measured biomarkers might predict clinical outcomes in patients with CKD and may be useful for individual risk profiling. Furthermore, early management may provide an opportunity to better patient survival.

Longitudinal effects of modified creatinine index on all-cause mortality in individuals receiving hemodialysis treatment.

BACKGROUND: The modified creatinine index (mCI), as a surrogate marker of muscle mass, has been associated with poor outcomes in patients undergoing hemodialysis. However, a single assessment may not reflect the clinical significance before an adverse clinical endpoint. OBJECTIVE: Analyze mCI trajectories and their association with all-cause mortality in incident hemodialysis patients. DESIGN: Retrospective observational cohort. SETTING: Outpatient dialysis facility. PATIENTS AND METHODS: We followed a cohort of patients who underwent maintenance hemodialysis treatment at least three times weekly for at least three months from 19 June 2010 to 29 December 2017. Clinical and laboratory features were measured at baseline. Longitudinal changes in the mCI were modeled using a joint longitudinal and survival model adjusted for baseline covariates and body mass index trajectories. MAIN OUTCOME MEASURE: All-cause mortality. SAMPLE SIZE: 408 with 208 males (50.7%). RESULTS: The mean (SD) age was 62.2 (12.3) years. The mCI changes were evaluated for a median (interquartile range) follow-up of 2.16 (1.13, 3.73) years. Forty-six percent (n=188) of patients reached the endpoint. A steeper slope (per 0.1 unit increase in the decrease rate) in modified creatinine index was associated with increased risk of all-cause mortality (HR, 1.04; 95% CI, 1.02-1.07; P=.011). In addition, an annual 1 mg/kg/day decrease in modified creatinine index level increased the hazard of all-cause mortality by 4% (HR, 1.04; 95% CI, 1.02-1.07; P=.001). LIMITATIONS: Residual kidney function was not observed in the data. Setting was single center and thus results may not be generalizable to other populations. CONCLUSION: All-cause death was significantly associated with loss of muscle mass over time. Longitudinal trajectories of nutritional markers may predict the clinical outcomes in patients undergoing hemodialysis. This may also be valuable for individual risk stratification. Furthermore, early management may provide an opportunity to improve patient survival. CONFLICT OF INTEREST: None.

Is White Blood Cell Count Associated With Mortality in Peritoneal Dialysis Patients?: A Retrospective Single-Center Analysis.

Objective White blood cell (WBC) count was used as a predictor in researches since it is a prognostic indicator and a substantial predictor of the development of cardiovascular disease (CVD). There have been very few reports looking at the association between WBC count and overall mortality in peritoneal dialysis (PD) patients. We intended to explore if the baseline total leukocyte count is linked to all-cause mortality, considering the association for linearity in PD patients. Material and methods The study comprised 204 incident PD patients who began treatment at the Nephrology Department of Health Sciences University, Kayseri Medical Faculty, Kayseri City Hospital between January 2009 and December 2017. The research period ended in January 2018. The link between baseline WBC count and all-cause mortality was studied using Cox proportional hazards models. Results The average age of the patients was 46.75 (8.49) years, and 48.5% were male. Diabetes and hypertension were prevalent in 59.8% and 76% of the population, respectively. The average WBC count was 9.37 (2.70) × 103/µL. The mortality risk increased by 23% for every one-unit increase in the crude model. The hazard of death in the fully corrected model was 1.12 [95% confidence interval (CI): 1.02-1.23, p = 0.015]. In the models with WBC count stratified by tertiles, the mortality hazard of patients in tertile 2 was 2.38 (95% CI: 1.24-4.58, p = 0.009) and of patients in tertile 3 in the fully adjusted model was 2.64 (95% CI: 1.30-5.33, p = 0.007), compared with patients in tertile 1. Conclusion The initial WBC count may have a long-term impact on patient survival. Individuals with higher basal values or even an elevation in follow-up should therefore be strictly controlled, and all preventative measures should be made to lower the risk level.

Lower serum albumin level is associated with increased risk of hospital admission and length of stay in hospital among incident hemodialysis patients by using overdispersed model.

Serum albumin is a major determinant of hospitalization in patients with end-stage renal disease (ESRD). Previous reports generally use the Poisson model to evaluate the relationships between outcome and response variables. However, hospitalization data are often overdispersed, and few studies using appropriate methods exist in the literature.This retrospective cohort study included 426 patients with ESRD receiving hemodialysis treatment between 2014 and 2018. Using a negative binomial regression model with hierarchical multivariable adjustments, we investigated the relationship between serum albumin, hospital admissions, and total hospitalization days. Mean age and mean baseline serum albumin levels were 64.7 ± 11 years and 3.5 ± 0.5 g/dL, respectively. At least one hospitalization was identified in 402 (94%) patients. The incidence rate was 1.48 (95% CI, 1.41-1.56) admissions per patient-year during the follow-up period of 5 years. A negative linear association was observed between serum albumin and hospitalization frequency. Hospitalization rates (95% CI) were 1.81 (1.65-1.98), 1.44 (1.3-1.59), 1.36 (1.22-1.51), and 1.33 (1.2-1.48) per patient-year in serum albumin levels ≤3, 3.1 to ≤3.3, 3.4 to ≤3.7, and ≥3.8 g/dL, respectively. Case mix-adjusted incidence rate ratio was 0.82 (95% CI, 0.70-0.94), while it was robust to further adjustments for malnutrition and inflammation markers. Similar results were observed in hospitalization days and time to the first hospitalization. These findings, which result from the negative binomial model using overdispersed data, suggest that lower serum albumin is related to increased hospitalization rates and hospital days in incident hemodialysis patients.

Serum Albumin Trends in Relation With Prognosis of Individuals Receiving Hemodialysis Therapy.

Introduction Hypoalbuminemia is recognized as an indication of protein-energy depletion in several disease states. According to many studies, hemodialysis (HD) patients who have decreased baseline serum albumin levels exhibit a poor prognosis. However, serum albumin does not stay at a constant level with the progress of the disease, considering that only a baseline value may not precisely reflect prognostic value. The study objective was to ascertain whether there is a link between serum albumin trajectories and all-cause mortality in incident HD patients.  Methods Retrospective cohort analysis was conducted in the HD unit at the University of Health Sciences, Kayseri Training and Research Hospital, Nephrology Clinic between June 19, 2010, and December 29, 2017. A total of 408 individuals aged 18 years or older, who had at least one measurement of serum albumin at baseline, were enrolled. The outcome was all-cause death. Time-dependent Cox regression and joint model were used to investigate the associations between serum albumin trend in time and the risk of all-cause mortality. Results Mean (SD) age was 62.17 (12.33) years, and 50.7% were male. At baseline, the mean (SD) albumin level was 3.59 (0.27). A faster decrease (per 1-SD increase in negative slope) in serum albumin levels was associated with increased risk of all-cause mortality (HR, 1.63; 95% CI, 1.08-2.84; p=0.023) in a fully adjusted joint model with slope parameterization. Also, an annual 1-SD increase in albumin level declined the hazard of all-cause mortality by 22% (HR, 0.78; 95% CI, 0.66-0.92; p=0.008) in a fully adjusted joint model with value parameterization. Similar results were obtained from time-dependent Cox models. Conclusion These findings suggest that longitudinal albumin evaluation, including the rate of change as a slope parameter, may be valuable for risk stratification of patients receiving HD.

Development of Immunoglobulin M Nephropathy in a Pregnant Woman.

Immunoglobulin M nephropathy (IgMN) is a glomerular disease that may be identified in all age groups, but children and young adults appear to have been affected more frequently in some series. The clinical picture could differ from hematuria to rapidly progressive glomerulonephritis. The main characteristics in pathologic examination are mesangial hypercellularity with a diffuse and granular immunoglobulin M deposition in the glomerular structure. To date, a standardized protocol has not been proposed for IgMN treatment. Systemic corticosteroids, calcineurin inhibitors, cyclophosphamide, and rituximab were agents reported in the literature. We present a 30-year-old woman admitted to the hospital for edema in the lower extremities at the 31st week of pregnancy. She had one abortus previously, and this was her second pregnancy. Renal biopsy performed after delivery was reported as IgMN with mesangial proliferation. She received 1 mg/kg/day prednisone therapy achieving complete remission. This report is the first case of IgMN developed in pregnancy.

The Relationship Between Hand Grip Strength and Nutritional Status Determined by Malnutrition Inflammation Score and Biochemical Parameters in Hemodialysis Patients.

OBJECTIVE(S): In hemodialysis patients, malnutrition and inflammation are prominent determinants of mortality. Reduced muscle mass is considered to be one of the most valid criteria in malnutrition diagnosis, and hand grip strength (HGS) is used as an efficient tool for evaluating muscle functioning. The aim of this study was to determine if HGS is associated with the nutritional status determined with malnutrition-inflammation score (MIS) and biochemical parameters in HD patients. DESIGN AND METHODS: Patients who have been on hemodialysis treatment for at least 6 months were included in this cross-sectional study. HGS was measured by a hand dynamometer. MIS was used to evaluate malnutrition, and Modified Charlson Comorbidity Index was used to rank comorbidities. RESULTS: A total of 132 hemodialysis patients, 73 (55.3%) males and 59 (44.7%) females, were included. The mean age of the patients was 56.90 ± 13.73 years. The mean age was 60.66 ± 13.42 years in the low-HGS group and 52.91 ± 13.00 years in the high-HGS group. HGS significantly decreased as age increased (P = .001). In patients with diabetes mellitus, HGS was significantly lower (67.4% and 43%; P = .013). Male patients with high HGS had significantly higher body weight (74.75 kg and 66 kg; P = .012). But there was no significant relationship between HGS and weight for female patients. HGS decreased when Charlson Comorbidity Index score (5 in low-HGS group and 4 in high-HGS group) and MIS values increased (8 in low-HGS group and 6 in high-HGS group) (P = .001 and P < .001, respectively). Only MIS was observed to have a statistically significant impact on HGS in the regression model (P < .001). CONCLUSION: A significant relationship was found between MIS and HGS; HGS's relationship with comorbidities was also presented in our study.

Serum bilirubin level and its impact on the progression of chronic kidney disease.

PURPOSE: To examine whether an elevated serum total bilirubin level affects the decline in renal function or new-onset chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (DM2). METHODS: This was a longitudinal observational study in patients who presented at the University of Health Sciences Hospital in Kayseri. Five hundred twenty-nine patients with DM2 who had conserved renal function were enrolled (estimated glomerular filtration rate > 60 ml/min/1.73 m2). Arising CKD stage 3 was the outcome measure. The patients were separated into three groups based on the total serum bilirubin levels. The first group (G1) ranged from 0.1 to 0.3, the second (G2) 0.4-0.5, and the third (G3) 0.6-0.9 mg/dl. The effect of total serum bilirubin levels on CKD 3 development was assessed using Cox proportional hazards regression. RESULTS: The risk of the CKD stage 3 development was highest in G1 who has the lowest serum total bilirubin levels (G1 vs. G3; hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.21-3.36; p = 0.007). In addition, G2 had a significant risk of CKD stage 3 development (G2 vs. G3; hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.08-2.32; p = 0.018). In the adjusted analysis, compared to G2 and G3, G1 had the highest risk (G1 vs. G3; hazard ratio [HR], 2.20; 95% confidence interval [CI] 1.29-3.77; p = 0.004). Similarly, G2 had a higher risk compared to G3 (hazard ratio [HR], 1.57; 95% confidence interval [CI] 1.05-2.34; p = 0.028). CONCLUSIONS: Serum bilirubin may predict the progression of CKD in patients with type 2 diabetes and preserved kidney function.

The effect of systemic erythropoietin treatment on retinal nerve fiber layer parameters in patients with chronic renal failure undergoing peritoneal dialysis.

PURPOSE: To evaluate the effect of erythropoietin (EPO) treatment on retinal nerve fiber layer (RNFL) parameters in patients with chronic renal failure (CRF) undergoing peritoneal dialysis (PD). METHODS: Fifty-eight eyes of 29 patients with CRF undergoing PD were evaluated. Fifteen patients have been treated with EPO (group 1), 14 patients without EPO treatment (group 2), and 30 eyes of 15 age-matched normal control subjects were assessed in group 3. A complete ophthalmologic examination and RNFL measurements were performed for each patient after PD. Anemia parameters were also measured. RNFL thickness protocol was used to acquire circular scans of 3.4 mm in diameter around optic nerve. RNFL thicknesses were evaluated in 4 quadrants. Only the left eyes were recruited for statistical analysis. The mean and quadrantal RNFL thickness values in group 1 were compared with those of groups 2 and 3. RESULTS: The mean RNFL thickness values in patients undergoing PD were statistically lower than the control group at superior, inferior, nasal, and temporal quadrant, respectively (P=0.03, 0.04, 0.04, and 0.03). Differences between the RNFL thickness values in group 1 and group 2 were statistically significant only in the temporal quadrant (P=0.02). CONCLUSIONS: In patients with CRF undergoing PD, RNFL thickness parameters were found to be significantly reduced. The effect of EPO on RNFL parameters was statistically significant only in the temporal quadrant.

Combined immune thrombocytopenic purpura and immunoglobulin A nephropathy: a similar pathophysiologic process?

IgA nephropathy is one of the most common forms of glomerulopathies. It is an immune complex-mediated glomerulonephritis diagnosed by the presence of mesangial IgA deposits that are often associated with mesangial cell proliferation. The IgG, C3, IgM, or other immunoglobulin light chains may be co-existed with IgA. Its pathogenesis suggested that it is responsible for enhancing the production of proinflammatory cytokines, chemokines, and growth factors. Platelet-derived growth factor (PDGF) has also been implicated as a modulator of disease activity. Immune thrombocytopenic purpura (ITP) is a bleeding disorder caused by thrombocytopenia that is not associated with a systemic disease. Its pathogenesis suggested an autoimmune disease in which IgG is thought to damage megakaryocytes, which are the precursors of platelet cells. Several studies reported that PDGF levels were higher in normal subjects than in patients with ITP. Moreover, ITP is a disease related to the antibody. Thus, our aim is to examine whether a similar pathophysiological relationship exist between ITP and IgAN that may be mediated by PDGF and/or IgG.

The biochemical and histopathological investigation of amlodipine in ethylene glycol-induced urolithiasis rat model.

BACKGROUND: Urinary calculi are a common and severe problem, which are formed by urolithiasis or by the formation of calcium oxalate (CaOx) crystals in the kidneys. Many treatment options such as drugs, various herbal preparations, surgical removal of the stones, and extracorporeal shock wave lithotripsy have been applied for this condition. The aim of this study is to assess the effects of the drug amlodipine in an experimentally induced urolithiasis rat model. MATERIALS AND METHODS: The effect of 5 mg/kg amlodipine was studied in rats that were first treated with 1% ethylene glycol and 1% ammonium chloride for 21 days to induce urolithiasis. The weight differences and the levels of calcium, magnesium, and phosphate were measured in serum and urine. In addition, urine CaOx level was defined and histopathological analyses were performed on the kidneys. RESULTS: Urolithiasis caused a significant increase in both serum and urine parameters compared with healthy rats. Urolithiasis plus amlodipine administration increased the levels of these same parameters. Urine CaOx level was high in urolithiasis rats and was also increased by urolithiasis plus amlodipine administration. The weight of the rats decreased in the urolithiasis plus amlodipine group when compared with the urolithiasis group. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in the urolithiasis group and the amlodipine treatment group. CONCLUSION: We showed that amlodipine may increase susceptibility to urolithiasis by raising hyperoxaluria and hypercalciuria. Further studies should be performed to elucidate the urolithiasis activity of amlodipine and to confirm the data.