Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Change in glucose intolerance status and risk of incident cardiovascular disease: Tehran Lipid and Glucose Study

Background: To assess the impact of changes in different glucose tolerance states on risk of incident cardiovascular disease (CVD)/coronary heart disease (CHD). Methods: A total of 4094 Iranians (43.9 men) aged � 30 years, without diabetes and CVD at enrolment were included. The following categories were defined both at baseline visit and 3 years later (second visit): normal fasting glucose (NFG), normal glucose tolerance (NGT), NFG and NGT (NFG/NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG and/or IGT (IFG/IGT). Changes in the categories, i.e. regression to normoglycemia, remaining in previous status and progression to diabetes were assessed. We used Cox's proportional hazard models adjusted for traditional risk factors and their changes, to estimate the hazard ratio (HR) with 95 confidence interval (CI) of different changing categories for incident CVD/CHD. Results: During a median follow-up of 12.42 years, 428 subjects (men = 265) experienced CVD. Considering persistent NFG/NGT as reference, participants who shifted from NFG/NGT to IFG/IGT showed a lower hazard of CVD in the fully adjusted model, HR 0.72 95% CI 0.52-0.996, P = 0.048. Moreover, subjects who shifted from IFG, IGT and IFG/IGT to diabetes had an increased risk of CVD/CHD. The risk however, was only statistically significant for those with IFG/IGT, 1.61 (1.03-2.51), P = 0.04 for CVD and 1.75 (1.10-2.78), P = 0.02 for CHD; considering IFG/IGT at both visits as reference. Furthermore, those who regressed from IFG/IGT to normoglycemia were at the same risk as those remained in IFG/IGT state, 1.12 (0.79-1.60), P = 0.52 for CVD and 1.04 (0.70-1.53), P = 0.85 for CHD. Among a subgroup of population with insulin data (n = 803) those with insulin resistance (IR) that converted to diabetes showed a higher risk for CVD, 3.68 (1.49-9.06), P = 0.01 and CHD, 2.76 (1.00-7.60), P = 0.05 events in the fully adjusted model. Conclusions: Among participants with IFG, IGT or IFG/IGT at baseline, only those who developed diabetes had a higher risk of developing CVD/CHD. Persistent IFG/IGT was not associated with higher risk, compared with those reverted to normoglycemia. Moreover, subjects who converted from NFG/NGT to incident IFG/IGT showed a signal for lower risk of CVD/CHD. © 2020 The Author(s)

Prevalence of JC polyomavirus large T antigen sequences among Iranian patients with central nervous system tumors

The human neurotropic JC virus (JCV) is of significant interest due to its experimental neuro- oncogenic potential. In clinical samples from human central nervous system (CNS) tumors, detection of JCV sequences suggests a possible association with CNS neoplasms, but the results are discrepant worldwide. To assess the prevalence of JCV sequences in Iranian patients with primary and metastatic CNS malignancies, a total of 58 fresh CNS tumors were examined by quantitative real-time PCR targeting the JCV large T antigen (LT-Ag) gene, and JCV DNA load was determined as viral copy number per cell. All patients were immunocompetent, and none of them had received immunosuppressive therapy before surgical operation. JC virus LT-Ag sequences were found in a total of 15 (25.9 ) out of the 58 tested samples. In primary CNS tumors, JCV sequences were identified more frequently in meningiomas (50.0 ) and schwannomas (35.7 ). In metastatic CNS tumors, JCV LT-Ag was identified in one case with brain adenocarcinoma originating from lung cancer. No statistically significant association between JCV positivity and various types of CNS malignancies was observed (P = 0.565). The mean JCV LT-Ag copy number in 15 positive cases was 1.8 � 10�4 ± 4.5 � 10�4 copies per cell (range 1.0 � 10�5-1.78 � 10�3 copies per cell). An inverse correlation between white blood cell (WBC) count and JCV copy number was observed, but this correlation was not statistically significant (R = �0.198, P = 0.480). This study provides the first data on the prevalence of JCV in primary and metastatic CNS tumors from Iranian patients. © 2014, Springer-Verlag Wien