Challenges in predictive modelling of chronic kidney disease: A narrative review.

The exponential rise in the burden of chronic kidney disease (CKD) worldwide has put enormous pressure on the economy. Predictive modeling of CKD can ease this burden by predicting the future disease occurrence ahead of its onset. There are various regression methods for predictive modeling based on the distribution of the outcome variable. However, the accuracy of the predictive model depends on how well the model is developed by taking into account the goodness of fit, choice of covariates, handling of covariates measured on a continuous scale, handling of categorical covariates, and number of outcome events per predictor parameter or sample size. Optimal performance of a predictive model on an independent cohort is desired. However, there are several challenges in the predictive modeling of CKD. Disease-specific methodological challenges hinder the development of a predictive model that is cost-effective and universally applicable to predict CKD onset. In this review, we discuss the advantages and challenges of various regression models available for predictive modeling and highlight those best for future CKD prediction.

Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study.

Objective: Loss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD). Methodology: The cross-sectional study included individuals who reported having no evidence of chronic kidney disease (CKD). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to assess kidney function. eGFR was calculated using the 2009 CKD-EPI (CKD-Epidemiological) equation. WT1 was analyzed in uE from humans and Wistar rats (before and after the 9th week of diabetes, n = 20). uE-WT1, urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were estimated using ELISA. The Kruskal-Wallis H test, Mann-Whitney U test, and stepwise multivariable linear regression were performed. Results: Urine NGAL and ACR increase with uE-WT1 quartiles (n = 146/quarter). Similarly, uE-WT1, KIM-1, and NGAL were positively associated with ACR. Furthermore, KIM-1, NGAL, and uE-WT1 correlated with ACR. uE-WT1 outperformed KMI-1 and NGAL to explain ACR variability (25% vs. 6% or 9%, respectively). Kidney injury in streptozotocin-induced diabetic rats was associated with a significant rise in uE-WT1. Moreover, the findings were confirmed by the histopathology of kidney tissues from rats. Conclusion: uE-WT1 was strongly associated with kidney function in rats. In individuals without CKD, uE-WT1 outperformed NGAL as a determinant of differences in ACR.

Use of Oral Empagliflozin to Obtain Optimal Blood Sugar Levels for Conducting 18 F-FDG PET-CT in Patients with Hyperglycemia-A Pilot Study.

Background Flourine-18 fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET-CT) is a well-established imaging modality for the evaluation of patients with oncological and nononcological conditions. The underlying principle of imaging is the preferentially increased glucose consumption by cancer cells, due to overexpression of glucose type 1 receptors that are insulin independent. Thus, one of the factors that leads to decreased sensitivity of an 18 F-FDG PET-CT is elevated blood sugar levels, leading to decreased glucose uptake by cancer cells due to competitive inhibition. A significant percentage of patients scheduled for PET-CT scan has diabetes mellitus type II as a comorbid condition and often has elevated random blood sugar (RBS) precluding an upfront PET-CT evaluation. Such cases must be rescheduled. This causes delay in the evaluation and management of such patients. Empagliflozin is a novel sodium glucose type 2 inhibitor that prevents tubular reabsorption of glucose and increases renal glycosuria resulting in decreased blood sugar. This drug does not cause significant hypoglycemia or increase endogenous insulin secretion. This study was undertaken to evaluate a potential role for empagliflozin in facilitating optimal blood sugar control in patients with hyperglycemia on the day of the scheduled PET scan. Methods This is an interventional prospective study and patients detected to have RBS more than 200 mg/dL on the day of the scheduled scan were included in the study. The patients were administered two tablets of 10 mg empagliflozin and kept under observation. Samples for RBS were taken at approximately 2nd and 4th hour post administration by bedside method. These patients underwent scan on the same day after adequate sugar control and when an RBS of less than 200 mg/dL was achieved. The primary outcome studied was change in RBS values in the patient cohort and evaluation of PET SUV (standardized uptake value) compared with the rest of the patients scheduled on the same day. Secondary outcome was assessment of any side effects in the patients. Results Total of 10 patients were found to have elevated blood sugar (RBS > 200 mg/dL; irrespective of being on medication) and did not meet the evaluation criteria for a PET-CT scan on the scheduled day. Following administration of the drug, all 10 patients were able to attain blood sugar levels and fulfill the criteria for undergoing a PET-CT scan. No obvious side effect was noted in any of the patient. The SUV values of the patient cohort were comparable with the rest of the patient scanned on the day. Conclusion In this pilot study, 20 mg of empagliflozin (2 tablets of 10 mg) appears to be a safe and effective method for achieving optimal decrease in the RBS without causing hypoglycemia or hyperinsulinemia. It can be safely employed in the subset of population with RBS between 201 and 300 mg/dL to adequately bring the sugar levels at acceptable levels RBS less than 200 mg/dl and fulfill the FDG PET-CT criteria as per European Association of Nuclear Medicine (EANM) norms.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

PURPOSE: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. METHODS: A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. RESULTS: Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. CONCLUSION: Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Kidney disease burden in an Asian Indian population: Effect of the new 2021 serum creatinine CKD-EPI equation.

AIMS: CKD-EPI (chronic kidney disease-epidemiological) serum creatinine equation is widely accepted for calculating estimated glomerular filtration rate (eGFR). The effect of transitioning from the older 2009 to the newer race-independent 2021 CKD-EPI equation on the estimated kidney disease burden (eKDB) was studied in an Asian-Indian population. METHODS: The study included 1156 adults, the two equations were compared for agreement (Bland-Altman and Cohen's kappa) and concordance (Lin's correlation and test for proportions). RESULTS: The 2021 CKD-EPI increased the eGFR (positive-bias), independent of age-group, gender or presence of type 2 diabetes mellitus (T2DM) and hypertension (HTN). Thus, the eKDB was significantly decreased by 2021 CKD-EPI equation. The agreement was highest for the age-group 31-40 years (95.8 % versus 87.5 % for > 50 years). Besides, the eGFR category was shifted from G3 to G1 in 8.2 % (95 % CI: 6.8-9.9) individuals by 2021 CKD-EPI. The effect of transition on eKDB was greater in individuals > 50 years (7.4 %) or with HTN (6.3 %). CONCLUSION: In comparison to the old equation, the 2021 CKD-EPI equation increased the eGFR, lowering the eKDB in this Asian-Indian cohort. The degree of lowering was affected by age-group, and presence of T2DM /HTN, but independent of gender.

Model for Early Prediction of Preeclampsia: A Nested Case Controlled Study in Indian Women.

Purpose: Preeclampsia (PE) affects 5-7% of the pregnancies worldwide, and is one of the most dreaded disorders of pregnancy contributing to maternal and neonatal mortality. PE is mostly presented in the third trimester of pregnancy. Here, we used serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to develop a model for predicting PE in Indian women in early second trimester. Methods: In this case-control study, a total 1452 healthy pregnant women were recruited. Blood samples were collected at the following gestational weeks (GWs), 12-20 (GW1), 21-28 (GW2) and 29-term (GW3), and post-delivery. Body mass index (BMI) was calculated by anthropometric measurements. Serum sFlt-1, PIGF and VEGF were analyzed by ELISA. A predictive model for PE was developed using multivariable logistic regression analysis. Results: In PE cases, serum PlGF and VEGF levels were significantly lower at each GW, while serum sFlt-1 was lower only at GW1, relative to age-matched controls, (n = 132/group). Age-matched comparison between PE cases and controls indicated that sFlt-1 was associated with decreased PE outcome (Odds ratio. OR = 0.988, CI = 0.982-0.993), whereas sFlt-1/PlGF ratio (OR = 1.577, CI = 1.344-1.920) and BMI (OR = 1.334, CI = 1.187-1.520) were associated with increased PE outcome. Logistic regression was used to develop a predictive model for PE at GW1. Using testing dataset, model was externally validated which resulted in 88% accuracy in predicting PE cases at 0.5 probability cutoff. Conclusion: Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20 weeks in women with optimal sensitivity and specificity.

Association of kidney functions with a cascade of care for diabetes and hypertension in two geographically distinct Indian cohorts.

AIM: Type 2 diabetes (T2DM) and hypertension (HTN) are the main modifiable risk factors of chronic kidney disease (CKD), among the known traditional and non-traditional risk factors. METHODS: We determined the prevalence and care-cascade of these modifiable CKD-risk factors and their association with socioeconomic status in adjoining Lucknow and Puducherry cities of India. RESULTS: 439 participants reported no CKD were recruited. Serum analysis revealed an Estimated Glomerular Filtration Rate (eGFR) ≥ 90 ml/min/1.73 m2 in 60.36% of the population. Of them, 55.85% had HTN and/or T2DM as CKD-risk factors; however, less than half of this population was unaware of their CKD-risk status. Awareness and treatment were significantly higher in Puducherry and were associated with literacy, occupation, and residence place. Although the CKD-risk population was about two times higher in Puducherry than Lucknow, the populations with mild-low eGFR were comparable in the two regions. Moreover, in Lucknow, mild-low eGFR and low awareness were more prevalent among the younger participants (<30 years), relative to Puducherry. CONCLUSIONS: Despite a higher prevalence of CKD-risk factors in Puducherry, populations with mild-low eGFR were comparable to Lucknow. More heightened awareness and better care cascade for CKD-risk factors in Puducherry may prevent or delay eGFR reduction.

The Impact of Double-Fortified Salt Delivered Through the Public Distribution System on Iodine Status in Women of Reproductive Age in Rural India.

BACKGROUND: Double-fortified salt (DFS) with iron and iodine has been demonstrated to be efficacious but questions of unintended effects on the gains in salt iodization remain. The main cross-sectional study based on the use of DFS over 1 y showed a reduction in iron deficiency risk. Whether the programs and the levels of added iron can adversely affect iodine status is yet to be established. OBJECTIVES: We hypothesized that the addition of iron to iodized salt can adversely affect iodine status in women of reproductive age (WRA). METHODS: A cross-sectional substudy was conducted in 4 matched-pair adjacent districts of rural Uttar Pradesh, India, in 2019. Under the public distribution system (PDS), DFS was available for 1 y through Fair Price Shops, in the 2 DFS supply districts (DFS-SDs). In these districts, iodized salt was also available in the market. In the 2 compared DFS nonsupply districts (DFS-NSDs), only iodized salt was available. In the substudy, participants included WRA (n = 1624) residing in rural areas of the selected districts. Iodine content in urine and salt samples was measured in each of the groups. RESULTS: Significantly fewer women from the DFS-SDs had median urinary iodine concentration values indicative of moderate to mild iodine deficiency compared with the women from the DFS-NSDs. The salt purchase pattern and iodine content revealed that significantly fewer (21.99%) households in the DFS-SDs were purchasing inadequately iodized crystal salt, compared with 36.04% households in the DFS-NSDs. CONCLUSIONS: The data reject the working hypothesis and suggest a beneficial effect of the DFS program on the iodine status in WRA, thereby supporting a recommendation of DFS supply through the PDS.

Quality of life among Oral Potentially Malignant Disorder (OPMD) patients: A prospective study.

OBJECTIVE: The purpose of this study was to evaluate the quality of life among the Oral Potentially Malignant Disorder (OPMD) patients during diagnosis, at one month and 3 months after intervention (surgical or conservative). METHODS: The University of Washington Quality of Life version (4UWQOL v4) and World Health Organization (WHO-BREF) were repeatedly administered on 54 OPMD patients. RESULTS: The results of Friedman's ANOVA showed a statistically significant change in the mean scores for pain, activity, speech, shoulder, taste, saliva, mood, and anxiety domains of UWQOL with time, (p-value <0.05); while physical health, social relationships, environment domains of WHO- BREF have shown significant changes in their respective mean scores. CONCLUSION: The assessment of Quality of Life (QOL) should routinely be done by the clinicians. If the clinicians start considering the QOL as the primary outcome of a treatment protocol, it will enhance patients' identity, well-being, and personality.

Metal-induced oxidative stress level in patients with fibromyalgia syndrome and its contribution to the severity of the disease: A correlational study.

BACKGROUND: Fibromyalgia syndrome (FMS) is an extra-articular rheumatological disease characterised by widespread chronic musculoskeletal pain. Metal-induced oxidative stress contributes to the severity of FMS. AIMS: First, this study evaluated the association between plasma levels of toxic heavy metals and essential metals with oxidative stress (OS) markers. Second, the OS markers and metal contents were correlated with the disease severity by assessing the Fibromyalgia Impact Questioner Revised (FIQR) and tender points (TP). METHOD: A total of 105 FMS patients and 105 healthy controls of similar age and sex were recruited. OS parameter such as lipid peroxidation (LPO), protein carbonyl group (PCG), nitric oxide (NO) and essential metals such as zinc (Zn), magnesium (Mg), manganese (Mn), copper (Cu) and toxic heavy metals such as aluminium (Al), arsenic (As), lead (Pb) were estimated. RESULTS: Levels of LPO, PCG, NO (p< 0.001) and Cu, Mn, and Al (p< 0.001), were significantly higher, and Mg (p< 0.001) and Zn (p< 0.001) were significantly lower in patients compared to controls. A positive association was observed between OS parameters, FIQR and TP with Cu, Al and Mn. A significant negative association was observed between Zn and Mg with FIQR, TP and OS parameters. CONCLUSION: Heavy metals such as Al induce OS parameters and decrease the levels of essential trace elements such as Mg and Zn, which may be responsible for the severity of FMS.

Nitric oxide, lipid peroxidation products, and antioxidants in primary fibromyalgia and correlation with disease severity.

BACKGROUND: Fibromyalgia syndrome (FMS) is characterized by altered pain perception with chronic, widespread musculoskeletal pain. The relationship between nitric oxide, oxidative stress and the severity of FMS has not been studied. This study evaluated NO levels in plasma, LPO products and antioxidants in Red Cell lysate in patients of FMS and correlated it with disease severity. METHODS: 105 FMS patients who fulfilled 1990 ACR Criteria and 105 age- and sex-matched healthy controls were recruited over two years from 2013 to 2015. Antioxidative enzyme activity was assessed by the estimation of catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) and superoxide dismutase (SOD). Nitric oxide in plasma, MDA marker of lipid per - oxidation (LPO) in the lysate was donen for estimating oxidative stress. FIQR was used to assess the severity of fibromyalgia. RESULTS: The catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase levels were significantly low in patients than controls (p<0.001). Plasma NO levels and LPO were also significantly high (p<0.05). NO and LPO levels showed a significant positive correlation with FIQR (r: 0.57, 0.8 and p: <0.001) whereas a negative correlation was observed between antioxidants (Cat, GR and GPx, but not SOD) and FIQR. CONCLUSIONS: Low antioxidants and raised LPO in RBC lysate in patients with FM together with high plasma NO correlated with the severity of FMS.

To evaluate the minimum number of renal scans required to follow pediatric patient postpyeloplasty.

The aim of the study is to evaluate the minimum number of renal scans required to follow pediatric patients postpyeloplasty. We prospectively reviewed the renal scans of 145 children with unilateral pelvi-ureteric junction obstruction who underwent dismembered pyeloplasty. Patients were then divided into four groups based on preoperative split renal function. All patients were followed with renal scan and ultrasound for minimum of 4 years. Renal scan and ultrasound were done after stent removal at 3, 6, and 12 months and then yearly after surgery. Drainage pattern (T1/2) was seen in all groups, except in patients where there was no comment on drainage pattern. Statistical analysis was performed using the Friedman ANOVA and Wilcoxon signed-ranks test as a post hoc test with Bonferroni correction and Kruskal-Wallis test with Mann-Whitney U-test as a post hoc test with Bonferroni correction. On comparison of the pattern of drainage with time in Groups 1-4, it was found that there was no significant difference with time in Group 1. Then, further, using Wilcoxon signed-rank test as post hoc test for Friedman ANOVA, Group 2 showed statistically significant difference in drainage pattern in scans between 6 months and 1 year, Group 3 showed statistically significant difference in drainage pattern in scans between 3 months and 1 year, and Group 4 showed statistically significant difference in drainage pattern in scans done between 3 and 6 months (P < 0.05). Minimum of three renal scans were required for paediatric patients post pyeloplasty at 3 months, 6 months and 1 year in the follow up period.

A Psychologic Assessment of the Parents of Patients With Cleft Lip and Palate.

The aim of this study was to evaluate the psychologic burden in terms of depression, anxiety, and stress among the parents of children with congenital craniofacial deformity, nonsyndromic cleft lip and/or palate (CL/P) with early and late diagnosis and/or treatment. In this study, total 240 patients were enrolled, out of which 72 were parents (either mother/father) of CL/P children, below 10 years (group A: before adolescence), 70 were parents of CL/P children, above 10 years of age (group B: after adolescence), and 98 were parents of children with no CL/P or any other genetic disorder (group C). Depression, anxiety, and stress scale-21 was administered in all groups after obtaining the informed consent. Mean ranks of group B revealed a higher score for all the 3 psychologic domains. The CL/P was further divided into only cleft lip, only cleft palate, and both cleft lip and palate groups. A statistically significant difference was observed in group B for all the psychologic domains. Analysis of variance was applied between the groups and a P-value <0.05 was considered as statistically significant. Analysis revealed severe to extremely severe depressed state of mind and moderate to severe levels of stress in maximum parents (above 20%) of group B. However, approximately 50% parents of group B showed extremely severe anxiety. Therefore, psychologic assessment helps in providing a psychiatric or psychologic counseling and treatment to the parents of CL/P children.