At later stages of chronic kidney disease (CKD), a pattern of linear and irreversible renal function decline is thought to be the most common. The objective of this study was to describe the characteristics of the different patterns of CKD progression, and to investigate potentially modifiable factors associated with the rate of decline of renal function. This was a retrospective, observational study in a cohort of adult patients with CKD Stage 4 or 5 not on dialysis. Decline in renal function was estimated as the slope of the individual linear regression line of estimated glomerular filtration rate (eGFR) over time. The following patterns of CKD progression were considered: unidentifiable, linear, nonlinear (curvilinear) and positive (improvement of renal function). The study group consisted of 915 patients (mean ±SD age 65 ± 14 years, 48% females, median follow-up time 16 months). A linear pattern was observed in 38%, unidentifiable in 23%, nonlinear in 24% and positive in 15% of the study patients. The mean eGFR slope was: −3.35 ± 4.45 mL/min/year. Linear and unidentifiable patterns were associated with more rapid loss of renal function. By multiple linear and logistic regression analysis, the magnitude of proteinuria, the systolic blood pressure and the treatment with dual renin–angiotensin system blockade were associated with more rapid CKD progression. On the contrary, older age and discontinuation of commonly prescribed medication with potential influence on renal function or eGFR measurements were associated with slower CKD progression. A majority of patients with advanced CKD show patterns of renal function decline different from linear, and several of the main determinants of CKD progression are potentially modifiable.
There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV‐seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12‐month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non‐CMV infection, graft loss, and all‐cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve‐month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS‐adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01–0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29–0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late‐onset disease.
Background. Hepatitis C virus (HCV) infection has been associated with an increased incidence of diabetes mellitus, both in the general population and among transplant patients. Methods. To test this hypothesis, we reviewed the records of 1614 patients who had undergone renal transplant at six Spanish centres between 1992 and 1998. We established the rate of onset of diabetes mellitus requiring >1 month of treatment with insulin (insulin‐treated diabetes mellitus, I‐TDM) among the 177 patients showing HCV antibody seropositivity at the time of transplant (HCV+ group). As controls, 177 HCV patients were selected who had received a kidney allograft immediately before or after the study patients at the same centre. Results. The HCV+ patients were well matched with controls in terms of characteristics (except a longer time on dialysis) and immunosuppressive treatment. After a mean follow‐up of 44 months, 28 cases of I‐TDM were diagnosed (9.6% in HCV+ and 6.2% HCV−, not significant (NS); odds ratio 1.6; 95% confidence interval 0.75–3.50). The onset of I‐TDM was somewhat later in HCV+ patients (467 days vs 292 days in HCV− patients, NS). Multivariate analysis identified the following prognostic factors for I‐TDM onset: age and BMI at the time of transplant, and polycystic kidney disease as the underlying cause of chronic renal insufficiency. No correlation was found with HCV positivity or time on dialysis. Conclusions. We were unable to confirm a greater incidence of post‐renal transplant insulin‐requiring diabetes in association with HCV infection. However, the observed tendency towards such an association suggests that the follow‐up period would need to be extended.
CMP is highly prevalent in patients with advanced CKD and is associated with other common symptoms of chronic uraemia. As with the general population, elderly age, the female gender, obesity and some comorbid conditions are the best determinants of CMP. Increased inflammatory markers commonly observed in patients with CMP may have a relevant role in its pathogenesis.
The cause of vitamin D deficiency in chronic kidney disease (CKD) is probably multi-factorial; however, the relative importance of each potential determinant is uncertain. To determine factors associated with serum levels of 25-hydroxy vitamin D (25OHD) and their relative importance in a cohort of pre-dialysis CKD patients. Incident patients admitted to a CKD outpatient clinic were included. Those who were receiving vitamin D supplements or anticonvulsants were excluded. In addition to demographic and clinical data, information about outdoor physical activity, season of blood collection, prescription of statins, anti-angiotensin drugs and xanthine-oxidase inhibitors were included as potential determinants. Johnson's relative weights analysis was used to estimate the relative importance of each potential determinant and the results were expressed as percentage contribution to multiple R. The study group consisted of 397 patients, 30 of whom were excluded. The mean serum level of 25OHD was 13.7±7.4ng/ml, and 81% of patients had serum levels lower than 20ng/ml. By multiple linear regression and relative weights analyses, the best determinants of low serum 25OHD levels and their relative importance were: higher proteinuria (28.5%), old age (21.4%), low physical activity (19.4%), female gender (19.3%) and low serum bicarbonate levels (11.4%). Proteinuria and age are the determinants with the highest relative importance for predicting 25OHD levels in CKD patients.
1 January 2016 in Molecular and Cellular Endocrinology