The Study of Correlation of Incidence, Severity of Renal, Cardiovascular Complications with Duration, Severity of Type 2 Diabetes Mellitus in a Tertiary Care Hospital

Background: Type 2 Diabetes Mellitus (DM) is a disorder of the endocrine characterised by hyperglycaemia which results from variable degrees of insulin resistance and insulin deficiency.Chronic hyperglycaemia in diabetes may lead to multi organ damage resulting in renal, cardiovascular and other complications.In our study, we aim to look for correlation between the degree of glycemic control, duration of type 2 DM, incidence, severity of renal, cardiovascular complications in type 2 DM patients. The objective of our study is to analyse the correlation between glycemic control and occurrence of cardiovascular, renal complications in type 2 DM patients. Materials and Methods: 50 type 2 DM patients were selected from the Medicine outpatient of Saveetha Medical College and Hospital from January 2021 to March 2021.The study was explained and informed consent was obtained. Ethical committee clearance was obtained.The duration of the disease, regularity of treatment are recorded, serum HbA1c was done to evaluate the degree of glycemic control.Renal function tests like estimation of urea and creatinine are done to look for renal complications. Echocardiogram was done to evaluate the cardiac status of the patient. Expected Outcome: We expect a direct correlation between the severity of uncontrolled hyperglycaemia, duration of the disease with the incidence of renal and cardiovascular complications. Results: 50 patients who were selected for the study having type 2 Diabetes Mellitus, were made into two groups - people with uncontrolled diabetes (HbA1c >7.5%) were more prone in developing renal and cardiac complications which were assessed by urea, creatinine, urine protein levels and ejection fraction (EF %) values. The significant cut off values to cause complications were taken as for urea (>40mg/dl), creatinine (>1mg/dl), urine protein (+/++/+++), EF value(>50%) and the presence/absence of regional wall motion abnormality (RWMA) was noted. It was also observed that longer age duration of the disease, more was the risk to develop cardiac complications than disease of shorter duration. Hence a poor control of hyperglycaemia made the subject prone to renal and cardiovascular complications. Conclusion: We arrive at a direct correlation between the severity and extent of uncontrolled hyperglycaemia with the incidence of severity and complications in the form of nephropathy and cardiac dysfunction.

Long-Term Preservation of Renal Function in Septic Shock Burn Patients Requiring Renal Replacement Therapy for Acute Kidney Injury

Background. The real impact of septic shock-associated acute kidney injury (AKI) on the long-term renal outcome is still debated, and little is known about AKI-burn patients. In a cohort of burn survivors treated by continuous renal replacement therapy (CRRT) and sorbent technology (CPFA-CRRT), we investigated the long-term outcome of glomerular and tubular function. Methods. Out of 211 burn patients undergoing CRRT from 2001 to 2017, 45 survived, 40 completed the clinical follow-up (cumulative observation period 4067 months, median 84 months, IR 44-173), and 30 were alive on 31 December 2020. Besides creatinine and urine albumin, in the 19 patients treated with CPFA-CRRT, we determined the normalized GFR by 99mTc-DTPA (NRI-GFR) and studied glomerular and tubular urine protein markers. Results. At the follow-up endpoint, the median plasma creatinine and urine albumin were 0.99 (0.72–1.19) and 0.0 mg/dL (0.0–0.0), respectively. NRI-GFR was 103.0 mL/min (93.4–115). Four patients were diabetic, and 22/30 presented at least one risk factor for chronic disease (hypertension, dyslipidemia, and overweight). Proteinuria decreased over time, from 0.47 g/day (0.42–0.52) at 6 months to 0.134 g/day (0.09–0.17) at follow-up endpoint. Proteinuria positively correlated with the peak of plasma creatinine (r 0.6953, p 0.006) and the number of CRRT days (r 0.5650, p 0.035) during AKI course, and negatively with NRI–GFR (r −0.5545, p 0.049). In seven patients, urine protein profile showed a significant increase of glomerular marker albumin and glomerular/tubular index. Conclusions. Burn patients who experienced septic shock and AKI treated with CRRT had a long-term expectation of preserved renal function. However, these patients were more predisposed to microalbuminuria, diabetes, and the presence of risk factors for intercurrent comorbidities and chronic renal disease.

miR-27b-3p is highly expressed in serum of patients with preeclampsia and has clinical significance

Background: Preeclampsia (PE) is defined as a salient complication of late pregnancy. microRNAs (miRNAs) have emerged as critical biological regulators in PE. This study determined miR-27b-3p expression in serum of PE patients and investigated its clinical significance in PE. Methods: Totally 130 pregnant women including 90 PE patients (51 mild PE and 39 severe PE) and 40 healthy controls were enrolled in this study. miR-27b-3p expression in the serum of PE patients and healthy controls was detected using RT-qPCR. The correlation among miR-27b-3p expression and 24-h urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine, and fetal birth weight was analyzed using Pearson's correlation coefficient. The targeting relationship between miR-27b-3p and PPARG was verified. PPARG protein level in PE patients was detected using ELISA kits. The predictive efficiency of miR-27b-3p and PPARG in PE was analyzed using the receiver operating characteristic (ROC) curve. Results: Compared to normal pregnant women, PE pregnant women, especially severe PE patients had higher miR-27b-3p expression. miR-27b-3p was positively correlated with 24-h urine protein, SBP, DBP, and serum creatinine, but negatively correlated with fetal birth weight. PPARG was poorly expressed in PE patients and negatively correlated with miR-27b-3p. ROC curve showed that both miR-27b-3p and PPARG had good predictive efficacy on PE. Conclusion: miR-27b-3p expression in serum of pregnant women with PE was positively correlated with the severity of PE symptoms, suggesting the involvement of miR-27b-3p in PE occurrence.

Decision Making for Anti-VEGF Inhibitor Continuation: Dip Stick? or Urine Protein/Creatinine Ratio? (VERSiON UP Study)

Background: Monitoring proteinuria is important for the management of patients with cancer treated with anti-vascular endothelial growth factor (VEGF) or anti-VEGF receptor (VEGFR) inhibitors (VEGF/Ri). Here we investigated the difference between the urine protein/creatinine ratio (UPCR) and a qualitative value test (QV) on the decision making of treatment continuation and the usefulness of UPCR testing in patients with gastrointestinal cancer treated with anti-VEGF/Ri.Methods: From January 2017 to December 2018, a survey was conducted based on the medical records of patients with gastrointestinal cancer with a QV of ≥ 2+ during the use of anti-VEGF/Ri at seven Japanese institutions participating in the Onco-nephrology Consortium. The primary endpoint was the ratio of the worst UPCR < 2.0 (low UPCR) in cases with a QV2+ at the point of the first proteinuria onset. The secondary endpoints were a comparison of low UPCR and worst UPCR ≥ 2.0 (high UPCR), the concordance rate between UPCR and QV in the Common Terminology Criteria for Adverse Events (CTCAE) grading, and the differences in the decision making for anti-VEGF/Ri continuation.Results: Among the 71 patients enrolled, the proportion of low UPCR in onset QV2+ (n = 53) was 66% (n = 35). In a comparison between low (n=36) and high UPCR cases (n = 24), body weight (P = 0.036), onset QV status (P = 0.0134), and worst QV status (P < 0.0001) were significantly associated with UPCR levels. The concordance rate for CTCAE Grade 2 of both the QV and UPCR was 83%. Regarding the judgment of anti-VEGF/Ri continuation, treatment was continued in 42.4% of cases when the QV became 3+, whereas only 25% continued treatment when the UPCR value became high.Conclusion: Urine dipstick test results may overestimate proteinuria, and the UPCR result tended to be more critical than the QV when deciding the treatment policy.Trial registration: This study is a multiple institutional retrospectively registered observational trial. Clinical Trial number: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (protocol ID UMIN000042545)

Diabetic Foot Ulcer Risk with Diabetic Kidney Disease and Renal Failure among 10,680 Patients

Objectives: Patients with Diabetic Kidney Disease (DKD) and foot ulcer have poor prognosis. However, no study have found association of diabetic foot ulcer (DFU) with diabetic kidney dysfunction and their co-existing risk factors. Materials and Methods: This cross sectional study collected the data for 10,680 patients for 15 years. All variables were analyzed biochemically and statistically by standardized methodology. Results: Levels of HbA1c, creatinine, systolic and diastolic blood pressures, microalbuminuria, spot urine protein, and spot urine protein to creatinine ratio were higher among the groups with foot ulcers (p-value < 0.0001 for all). Average ABI was observed to be lower among the groups demonstrating nephropathy and DKD (p=0.025 and 0.022 respectively. DFU was significantly associated with HTN (odds ratio 2.2; 95% CI 1.66 to 2.9; p < 0.0001), nephropathy (odds ratio 4.77; 95% CI 3.53 to 6.5; p < 0.0001) and DKD (odds ratio 4.77 and 6.83; 95% CI 4.6 to 10.2; p < 0.0001). HbA1c of 7.8% was 60% sensitive and 52% specific for the development of DFU. Creatinine of 1.2 mg/dl was 75% sensitive and 48% specific for DFU. Spot urine protein excretion from nephrons of 35 mg/dl was 88% sensitive and 90% specific for the development of DFU. Conclusion: Nephropathy/DKD are risk factors for the development of DFU. With optimal diabetes control, regular and routine assessment of the feet and early screening of diabetic patients for neuropathy, nephropathy, hypertension, dyslipidaemia and other diabetic complications are essential. Doi: 10.28991/SciMedJ-2021-0304-6 Full Text: PDF

Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

Spot Urine Protein Excretion in the First Year Following Kidney Transplantation Associates With Allograft Rejection Phenotype at 1-Year Surveillance Biopsies: An Observational National-Cohort Study

Introduction: Urine protein excretion is routinely measured to assess kidney allograft injury, but the diagnostic value of this measurement for kidney transplant pathology remains unclear. Here we investigated whether spot urine protein excretion in the first year following transplantation associates with allograft rejection phenotype at 1-year surveillance biopsies and de-novo occurrence of donor-specific antibodies (DSA).Patients and Methods: This prospective, observational national-cohort study included 139 non-sensitized patients who received a deceased donor kidney transplant between December 2014 and 2018. All patients received basiliximab induction and tacrolimus-based immunosuppression. Estimated protein excretion rate (ePER) was calculated monthly from spot urine protein-to-creatinine ratios. At 1-year, all recipients underwent surveillance graft biopsy and were screened for de-novo DSA. Screening-positive sera were subjected to single antigen bead (SAB) testing. The occurrence of de-novo DSA was determined based on SAB reactivity patterns using a mean fluorescence intensity threshold &gt;1,000.Results: Among the 139 study patients, 27 patients (19%) had histologic evidence of T cell-mediated rejection (TCMR), and 9 patients (7%) had histologic evidence of antibody-mediated rejection (AMR) at 1-year surveillance biopsy. One year after transplant, 19 patients (14%) developed de-novo DSA. Compared with patients without rejection and no de-novo DSA, mixed-effects linear regression analysis showed a significant difference in slope of ePER during the first year in patients with AMR and de-novo DSA at 1-year (46, 95% CI 25–68 mg/day/1.73 m2 per month and 34, 95% CI 20–49 mg/day/1.73 m2 per month, respectively). Patients with vascular TCMR also showed a significant difference in ePER slope over time compared with patients with non-rejection findings (31, 95% CI 9–52 mg/day/1.73 m2 per month). The discriminatory power of ePER for intragraft rejection processes was better in patients with AMR (AUC 0.95, 95% CI 0.90–0.99; P &lt; 0.001) than in those with TCMR (AUC 0.68, 95% CI 0.59–0.79; P = 0.002), with 89% sensitivity and 93% specificity for proteinuria &gt;550 mg/day/1.73m2.Conclusions: An increase in ePER in the first year following kidney transplantation associates with AMR, vascular TCMR and de-novo DSA at 1-year and may be used as a non-invasive clinical marker of intragraft endothelial cell injury.

Novel TBC1D8B Variant in a 6-Month-Old Boy With Steroid-Sensitive Nephrotic Syndrome: A Case Report

A structural abnormality or dysfunction of podocytes is the major cause of nephrotic syndrome (NS). The TBC1D8B protein interacts with nephrin, a podocyte slit diaphragm protein, regulates vesicle transport, and functions in the pathogenesis of NS. We report a novel potentially pathogenic variant in the TBC1D8B gene in a 6-month-old boy with NS. A 6-month-old boy was admitted to the hospital because of edema and fever. Our systematic examination led to a diagnosis of NS. Because of the early age of onset, we performed trio whole-exome sequencing of him and his parents. The results showed a new potentially pathogenic variant in the TBC1D8B gene on the X chromosome, c.2717A&gt;G (p.His906Arg). After routine glucocorticoid therapy, his urine protein turned negative, indicating steroid-sensitive NS. The new TBC1D8B variant identified here, c.2717A&gt;G (p.His906Arg), may be associated with early-onset NS in children. Although NS due to pathogenic variants in this gene is more commonly steroid-resistant, our patient had steroid-sensitive NS.

Comparisons of urine protein-to-creatinine ratios and their dynamic change patterns during labor at term between normal pregnant women and women with pregnancy induced hypertension

Objective to compare the urine protein-to-creatinine ratios (uPCRs) during labor at term between normal and women with pregnancy-induced hypertension (PIH), and to evaluate the patterns of change in uPCRs. Design observational study Setting Tertiary referral hospital in Taiwan Population normal pregnant or women only with PIH at term were enrolled Methods and Main outcome measures uPCRs in four phases (latent, active, recovery and early postpartum) and related clinical data at delivery were collected. Multivariate analysis with a linear regression model were performed to analyze continuous variables after adjusting for clinical data between two groups. Results 68 normal and 24 pregnant women with PIH were included. There were no differences in the uPCR or the proportion cases of uPCRs ≥ 300 mg/g between normal and PIH group in the latent, active, recovery or early postpartum phases. There was a statistically significant tendency for the proportion of uPCRs ≥ 300 mg/g to increase from the latent to the early postpartum phase in both groups. The proportion of uPCRs ≥ 300 mg/g significantly increased from the active to the recovery phase and then declined from the recovery to the early postpartum phase in normal pregnant women.Thus no differences in uPCRs cases change between any two phases in women with PIH, except the duration above stated. Conclusion. This is the first study to demonstrate that uPCRs data are not different between normal pregnant and PIH groups during the course of labor, but it did show different dynamic change patterns throughout the labor phases.