Methods: Primary data were collected through a standardized survey, and secondary data analysis was used to derive estimates of the ESRD expenditure.
Results: Total annual expenditure of ESRD by the public sector has grown 94% within a span of 7 years, from Malaysian Ringgit [MYR] 572 million (US dollars [USD] 405 million, purchasing power parity [PPP] 2010) in 2010 to MYR 1.12 billion (USD 785 million, PPP 2016) in 2016. The total ESRD expenditure in 2010 constituted 2.95% of the public sector's total health expenditure, whereas in 2016, the proportion has increased to 4.2%. Only 6% of ESRD expenditure was spent on renal transplantation, and the remaining 94% was spent on dialysis.
Conclusion: The share of ESRD expenditure in total health expenditure for the public sector is considered substantial given only a small proportion of the population is affected by the disease. The rapid increase in expenditure relative to the national total health expenditure should warrant the relevant authorities about sustainability of the existing financing mechanism of ESRD and the importance to institutionalize more drastic preventive measures.
Methods: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min.
Results: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85.
Conclusion: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology.
Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay. COL4A5 mRNA was measured using quantitative reverse transcriptase polymerase chain reaction. Endoplasmic reticulum (ER) size was measured on electron micrographs and after HSP47 immunostaining. Markers of ER stress (ATF6, HSPA5, DDIT3), autophagy (ATG5, BECN1, ATG7), and apoptosis (CASP3, BAD, BCL2) were also quantitated by quantitative reverse transcriptase polymerase chain reaction. Measurements were repeated after 48 hours of incubation with 10 mM sodium 4-phenylbutyrate acid.
Results: Both COL4A5 missense variants were associated with reduced proliferation rates on day 6 (P = 0.01 and P = 0.03), ER enlargement, and increased mRNA for ER stress and autophagy (all P values < 0.05) when compared with normal. Sodium 4-phenylbutyrate treatment increased COL4A5 transcript levels (P < 0.01), and reduced ER size (P < 0.01 by EM and P < 0.001 by immunostaining), ER stress (p HSPA5 and DDIT3, all P values < 0.01) and autophagy (ATG7, P < 0.01). Extracellular collagen IV α5 chain was increased in the M1 line only (P = 0.06).
Discussion: Sodium 4-phenylbutyrate increases collagen IV α5 mRNA levels, reduces ER stress and autophagy, and possibly facilitates collagen IV α5 extracellular transport. Whether these actions delay end-stage renal failure in men with X-linked Alport syndrome and missense mutations will only be determined with clinical trials.
METHODS: A total of 607 adolescents were recruited from the Malaysian Health and Adolescents Longitudinal Research Team (MyHeART) study, a prospective cohort study conducted from March 2012 to May 2016 that explored the noncommunicable diseases (NCDs) risk factors among 13 to 17 years old students in 3 states of Peninsular Malaysia. Students who participated in all 3 data collection periods in 2012, 2014, and 2016 with kidney function assessment across all 3-time points were included in the current study. The students' estimated glomerular filtration rate (eGFR) was calculated from isotope-dilution mass spectrometry-traceable Schwartz's equation and categorized based on Kidney Disease: Improving Global Outcomes (KDIGO) classification. Changes in kidney function were examined, and the longitudinal relationship between eGFR and multiple NCD risk factors was analyzed using the generalized estimating equation (GEE).
RESULTS: The prevalence of decreased eGFR (60-89 ml/min per 1.73 m2) among the students increased from 6.1% (2012) to 30.0% (2014) and 40.2% (2016). Based on the GEE, the student's eGFR decreased over time, with a steeper decline during early to midadolescence. Males and rural students had lower eGFR compared to their counterparts. Students who are morbidly obese had lower eGFR than those with normal body mass index (BMI). Protein consumption also has a potential moderating effect on eGFR in adolescents.
CONCLUSION: Kidney function changes can be detected as early as adolescence and are likely attributable to multiple NCD risk factors. Therefore, more comprehensive prevention efforts from various stakeholders are needed to identify health issues like CKD.
METHODS: We analysed the effects of adjudication of ~2100 maintenance kidney replacement therapy (KRT) and ~1300 major atherosclerotic events (MAEs) recorded in SHARP. We first compared outcome classification before versus after adjudication, and then re-ran randomised comparisons using pre-adjudicated follow-up data.
RESULTS: For maintenance KRT, adjudication had little impact with only 1% of events being refuted (28/2115). Consequently, randomised comparisons using pre-adjudication reports found almost identical results (pre-adjudication: simvastatin/ezetimibe 1038 vs placebo 1077; risk ratio [RR] 0.95, 95%CI 0.88-1.04; post-adjudicated: 1057 vs 1084; RR=0.97, 95%CI 0.89-1.05). For MAEs, about one-quarter of patient reports were refuted (324/1275 [25%]), and reviewing 3538 other potential vascular events and death reports identified only 194 additional MAEs. Nevertheless, randomised analyses using SHARP's pre-adjudicated data alone found similar results to analyses based on adjudicated outcomes (pre-adjudication: 573 vs 702; RR=0.80, 95%CI 0.72-0.89; adjudicated: 526 vs 619; RR=0.83, 95%CI 0.74- 0.94), and also suggested refuted MAEs were likely to represent atherosclerotic disease (RR for refuted MAEs=0.80, 95%CI 0.65-1.00).
CONCLUSIONS: These analyses provide three key insights. First, they provide a rationale for nephrology trials not to adjudicate maintenance KRT. Secondly, when an event that mimics an atherosclerotic outcome is not expected to be influenced by the treatment under study (e.g. heart failure), the aim of adjudicating atherosclerotic outcomes should be to remove such events. Lastly, restrictive definitions for the remaining suspected atherosclerotic outcomes may reduce statistical power.