Cause Of Chronic Kidney Disease Research Articles

MO727: Acute Myocardial Infarction in Diabetic Versus Non-Diabetic Haemodialysis Patients: A Single Centre 4-Years’ Experience

Abstract BACKGROUND AND AIMS Cardiovascular disease (CVD) is the leading cause of death among patients with end-stage renal disease accounting for 40% of all mortality. Diabetes mellitus, the main cause of chronic kidney disease (CKD) worldwide, together with obesity, hypertension and dyslipidaemia, places patients at higher risk for acute myocardial infarction (AMI). Effective treatment such as coronary revascularization is critical to lowering the subsequent risk of CV events and improving long-term survival. In this study, we aim to compare the cardiovascular outcomes in diabetic versus non-diabetic patients in dialysis following an AMI. Methods We retrospectively enrolled 70 CKD stage 5d patients (4 h/3 times a week) aged ≥ 18 years old who were admitted at the cardiac intensive care unit with AMI between January 2017 and December 2020. Baseline variables and laboratory data were collected at admission and 1 month after discharge for follow-up. Two groups were created: G1 (diabetic) and G2 (non-diabetic). Data were collected by consulting electronic medical records. Statistical analyses were performed using the SPSS statistics version 23.0. RESULTS Seventy patients (male: 72.9%) with a mean age of 70.9 ± 12 years were selected. G1 (n = 33; 47.1%) and G2 (n = 37; 52.1%) had similar distributions of gender (male: 72.7% versus 72.9%; P = 0.081) and age (70.9 ± 9 versus 70.8 ± 10 years; P = 0.076) opposite to dialysis vintage (33 versus 17 months; P = 0.003). The main CKD cause in G2 was hypertensive nephrosclerosis (n = 14, 37.8%), followed by uncertain aetiology (n = 10, 27.1%), obstructive uropathy (n = 6, 16.2%), autosomal dominant polycystic kidney disease (n = 3, 8.1%), IgA nephropathy (n = 2, 5.4%) and small vessel vasculitis (n = 2, 5.4%). Previous comorbidities were (G1 versus G2): arterial hypertension (93.9% versus 97.3%; P = 0.77), smoking habits (9.1% versus 16.2%; P = 0.033), heart failure (78.8% versus 67.6%; P = 0.064), left ventricular hypertrophy (47.9% versus 52.8%; P = 0.082), body mass index > 30 kg/m2 (57.6% versus 56.8%; P = 0.72) and dyslipidaemia (100% versus 99%; P = 0.91). At admission, groups were compared hypoalbuminemia (serum albumin < 3.0 g/dL) [37.9% versus 26.8%, OR 4.1, 95% confidence interval (95% CI) 2.1–24.4; P = 0.0022] and clinical frailty score > 4 points (56 versus 32%, OR 5.4, 95% CI 1.4–25.1, P = 0.0041). Total cholesterol (149 ± 38 versus 146 ± 39 mg/dL) and low-density lipoprotein cholesterol (97 ± 31.6 versus 94 ± 29.9 mg/dL) were also compared with no statistically significant differences. In G1, glycaemic control was satisfactory (HbA1c: 7.4%); 45.5% (n = 15) were taking insulin alone, 9.0% (n = 3) were taking oral antidiabetics (DPP-4 inhibitors) and 45.5% (n = 15) were using a combined therapy. Regarding AMI in G1 and G2, ST segment elevation myocardial infarction (STEMI) was present in 8 (24.2%) versus 11 (29.7%) patients (P = 0.08); all patients underwent coronary revascularization except 3 patients on each group (9% versus 8.1%), who had a NSTEMI. During hospitalization (10.5 ± 6 days versus 10.2 ± 12 days; P = 0.12), 13 patients died (n = 6; 18.2% versus n = 7; 18.9%, P = 0.07); 3 were treated conservatively and all 3 belonged to G1. The main cause of death was cardiogenic shock (n = 10, 83.3%). No deaths or new CV events occurred 30 days post-AMI. Multiple regression analysis showed that dialysis vintage was the only significant predictor for the occurrence of a CV event, regardless of being STEMI/NSTEMI or of any intervention. CONCLUSION Based on our results, G1 and G2 showed no difference in mortality or risk of developing a new CV event in the following month post-AMI. This might be related with several non-traditional risk factors, such as chronic volume overload, anaemia, inflammation, oxidative stress, and chronic kidney disease-mineral bone present in the majority of dialysis patients that were not evaluated or with the size of our sample.

MO393: Kidney Echogenicity and Kidney Length as Surrogate Markers of Kidney Function With an Increased Echogenic Pattern Being the Most Predictive of Renal Dysfunction, Particularly in HIV

Abstract BACKGROUND AND AIMS Non-communicable diseases (NCDs) are rapidly emerging as a major cause of chronic kidney disease (CKD) in Africa with a reported prevalence of 10.7% locally. At current, few high-quality studies assessing the epidemiology of CKD in South Africa have been published. Alarmingly, CKD is now at epidemic proportions and is a leading cause of mortality with significant cost implications. This study aims to investigate economic means of predicting renal function in CKD by exploring the association between estimated glomerular filtration rate (eGFR) and renal morphology evaluated by ultrasound (US). METHOD This is a retrospective descriptive chart review conducted at the Department of Nephrology, Inkosi Albert Luthuli Central Hospital (IALCH), Cato Manor, Kwa-Zulu Natal from January 2016 to December 2016. A total of 455 patients who had met the Kidney Disease Improving Global Outcomes (KDIGO) definition of CKD with eGFR (MDRD) and kidney US performed were included. Demographic, clinical, laboratory and kidney morphological data [kidney length (KL), increased echogenicity (IE) and loss of corticomedullary differentiation (LCMD)] on US were collected and analyzed with SPSS software (v. 27). Associations between eGFR, parameters on US and CKD risk factors were determined using logistic regression analysis. RESULTS Black Africans (75.2%; n = 342) and females (56.9%; n = 259) predominated the sample. Whilst, Indians, Whites and Coloreds comprised of 20.4%, 2.42% and 1.98% of the study respectively. The median age was 45.8 ± 14.3 years. Hypertension (34.9%), diabetes (26.8%), HIV (27.5%) and glomerulonephritis 9.89% were the four most frequently reported risk factors, of which Black Africans comprised more than 50% of cases (P < 0.001). A significant proportion of patients 65.7% (n = 307) had end-stage renal disease with a median eGFR of 14.4 ± 12.8mL/min/1.73m2 (P < 0.001). The median right and left KL were short at 8.49 ± 2.16 cm and 8.60 ± 2.20 cm respectively. Black Africans were also found to have significantly shorter KLs and lower eGFRs (P < 0.001). The dual effect of IE and LCMD predisposed to significantly shorter KLs and lower eGFRs than in the presence of one or no abnormality on US (P < 0.001). IE [−9.29 odds ratio (OR); 95% confidence interval (CI) (−13.8 to −4.77); P < 0.001] and KL [right: 5.02 OR; 95% CI (3.44–6.60); P = 0.04; left: 5.11 OR; 95% CI (3.56–6.66); P = 0.04] were found to be significant predictors of eGFR. HIV was the only risk factor found to be negatively associated with all determined measures of renal function, as well as the sole predictor of IE [2.31 OR; 95% CI (0.17–3.15); P = 0.02]. CONCLUSION The CKD epidemic is driven by the complex interplay between communicable (HIV) and NCDs (HPT/DM) and has emerged as important public health and economic threat in Southern Africa. Africans are most vulnerable presenting with an advanced and accelerated disease course. GFR determination and US are inexpensive means of determining renal function, particularly in resource-limited settings. IE and KL are surrogate markers of kidney function with an increased echogenic pattern being most predictive of kidney dysfunction in CKD, particularly in HIV.

End Stage Renal Disease among Patients Undergoing Haemodialysis at a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Chronic kidney disease is defined as structural or functional damage of the kidney persisting for three or more months. Studies have shown hypertension and diabetes as the leading causes of chronic kidney disease. The aim of this study is to find out the prevalence of end-stage renal disease patients undergoing haemodialysis in a tertiary care hospital. This was a descriptive cross-sectional study conducted among 96 patients undergoing haemodialysis from February 13, 2021 to April 4, 2021 in the hemodialysis unit of a tertiary care centre after receiving ethical clearance from the Institutional Review Committee (Reference number: 354). Convenience sampling was done and all patients older than 18 years who were on maintenance haemodialysis on an outpatient basis were included in the study. Data were collected using a self-administered questionnaire. Data were analysed using the Statistical Package for the Social Science version 22.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentages for binary data and mean with standard deviation for continuous data. Among 96 patients undergoing haemodialysis, the prevalence of end-stage renal disease was 83 (86.45%) (79.60-93.30 at 95% Confidence Interval). The most common underlying condition was hypertensive nephropathy in 34 (40.96%) patients, followed by both hypertensive and diabetic nephropathy in 26 (31.33%) patients. The prevalence of end-stage renal disease in our study was higher when compared to similar studies conducted in similar settings. Early diagnosis and adequate treatment of hypertension and diabetes could be crucial to reducing the prevalence of the end-stage renal disease. chronic kidney failure; chronic renal insufficiency; end stage renal disease; hemodialysis; Nepal.

Effects of Methanolic Extract of Moringa oleifera on an In Vitro Model of Diabetic Nephropathy

Diabetic nephropathy (DN) is a severe diabetic complication and a leading cause of chronic kidney disease and renal failure worldwide. The high prevalence of end stage renal disease (ESRD) due to diabetes, coupled with the lack of efficient treatments, prompts the need for newer therapeutic strategies that overcome the drawbacks of the existing ones. In recent years, Moringa oleiferahas been identified as a plant with multiple nutritional and medicinal advantages. Importantly, previous studies have reported antioxidant and anti‐hyperglycemic properties of Moringa leaf extracts in diabetic rats. The growing interest in the potential use of nutraceuticals over conventional drugs along with the recent evidence of the beneficial effects of M. oleifera extract led us to investigate the effects of the methanol extract of M. oleifera on an in vitro model of human glomerular epithelial cells (HGEC).HGEC were chronically cultured in the presence of physiological (5mM) or high glucose (25mM) levels and treated with different concentrations of methanolic extract of M. oleifera(MOE). We evaluated the effect of MOE on the production of advanced glycation end‐products (AGE), cell viability, and response to oxidative stress. Our results indicate that MOE can effectively inhibit AGE formation in vitro and provide a cytoprotective effect to cells following an oxidative challenge. However, in line with prior data indicating that HGEC chronically exposed to high glucose are primed for apoptosis, these cells showed reduced viability following exposure to MOE compared to cells exposed to normal glucose. These results suggest that acute, high doses of MOE might not be beneficial following chronic exposure of kidney cells to glucose, but the possibility of a protective effect of MOE when administered early is worth exploring.

Use of Continuous Glucose Monitoring in the Assessment and Management of Patients With Diabetes and Chronic Kidney Disease.

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to ‘burnt-out’ beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. RAS demonstrated a loss of medium-sized vessels (0.2-0.3 mm)comparedwithdonorkidneys (P=0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and environmental metals exposure on chronic kidney disease

Chronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is associated with the regulatory effects of NLRP3 gene polymorphisms. This study evaluated the association between NLRP3 gene polymorphisms and CKD, and further explored whether the association of environmental metals with CKD varied by the NLRP3 genotypes. A total of 218 CKD patients and 427 age- and sex-matched healthy controls were recruited in this clinic-based case–control study. Patients were identified as having CKD if their estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and stage 3–5 for at least 3 months. We examined the genotypes of fifteen common ssingle-nucleotide polymorphisms in NLRP3 genes. Concentrations of total urinary arsenic were examined by summing of urinary inorganic arsenic species. Concentrations of selenium, cadmium, and lead were measured from blood samples. Associations between NLRP3 polymorphisms, environmental metals exposure, and CKD were evaluated using multivariable logistic regression while controlling for confounders. We observed that the odds of carrying NLRP3 rs4925650 GA/AA genotypes, NLRP3 rs1539019 CA/AA genotypes, and NLRP3 rs10157379 CT/TT genotypes were significantly higher among CKD cases compared to controls, with the adjusted odds ratio (95% confidence interval) were 1.54 (1.01–2.36), 1.56 (1.04–2.33), and 1.59 (1.05–2.38), respectively. The significant multiplicative interactions were identified between high levels of blood lead and NLRP3 rs4925650 GA/AA genotypes; high levels of blood cadmium or low levels of plasma selenium and the NLRP3 haplotype (rs4925648, rs4925650, rs12048215, and rs10754555) C-A-A-C multiplicatively interacted to increase the risk of CKD. Our results imply that NLRP3 polymorphisms may play an important role in the development of environmental metals exposure related CKD.

Non-diabetic Kidney Disease in Diabetic Population: A Single-Center Study From South India.

Introduction: Diabetic kidney disease (DKD) is the commonest cause of chronic kidney disease and end-stage kidney disease worldwide, consequently it has become an important productive implication to the healthcare system. This study was conducted to assess the prevalence of non-DKD (NDKD) in diabetic patients from south India.Objective: To assess the prevalence of NDKD in type 2 diabetes mellitus patients presenting to a tertiary care hospital from south India and also to analyze clinical clues to establish a diagnosis of NDKD.Patient and methods: It is a retrospective observational study of analyzing patient characteristics and renal biopsies. All Diabetic patients with a clinical suspicion of non-diabetic kidney disease who underwent renal biopsy during the study period between January 2012 and June 2017 were included. Based on the biopsy findings, the patients were classified into three groups (isolated diabetic nephropathy, isolated NDKD, and NDKD with underlying diabetic nephropathy) and patients’ characteristics were compared between the groups for analysis.Results: A total of 236 renal biopsies were analyzed for the study. Of that, 114 had features of DKD, 78 NDKD with diabetic nephropathy (DN) and 44 had isolated NDKD. Acute interstitial nephritis was the most common cause of NDKD.Conclusion: From the current study, the long duration of diabetes mellitus beyond five years and hypertension beyond two years reasonably predict DKD.

The impact of hypertension and Age groups on the severity of chronic kidney disease and their associated with renal function test status

Chronic kidney disease is one of the renal disease conditions, slow development may take months and irreversible. Different factors can lead to chronic kidney disease, Hypertension known as one of the main causes of chronic kidney disease, vision loss, coronary artery disease and heart failure. Secondary hypertension is common in chronic kidney disease patients leading to end-stage renal disease (ESRD). This current study was conducted to evaluate the relative impact of HTN on CKD and ESRD risk in women compared with men. In this study, the prevalence of CKD among hypertensive patients was found to be 67. % . Also, current study demonstrated unequal impact of Hypertension on Age, Sex and the severity of chronic kidney disease and renal function test status.

IDF21-0171 Study of renal Profile In diabetic patient: Retrospective study among 48 patients

Background: Diabetes is considered the commonest cause of end-stage renal disease. The increasing incidence of obesity and an ageing population, together, will lead to a greater number of people with diabetes associated with chronic kidney disease that could either be secondary to diabetic nephropathy or of different aetiology. Based on data from the UK and USA, up to 40% of people with diabetes will develop chronic kidney disease. Pooled data from 54 countries reveal that more than 80% of cases of end-stage renal disease (ESRD) are caused by diabetes, hypertension or a combination of both. Aim: To study of renal profile in diabetic patient. Method: This was a retrospective analytical and descriptive study conducted at internal medicine department on 13 months. The total of 48 diabetic patients were included in this study. Patient data including patient characteristics, and hypertension, duration of diabetes, creatinine level, blood pressure, blood glucose level, HbA1c. The eGFR (Glomerular Filtration Rate) has been determined using the MDRD equation (Modification of Diet in Renal Disease). Renal disease was staged according to the 2012 High Authority of Health France guidelines. The statistical analysis was carried out using Epi-Info7 software. Results: There were 48 diabetic patients with a mean age of 66±10 years with male predilection (77%) compared to females (23%). Mean duration of diabetes mellitus was 15±9 years. Most of patients (93.75%) were type2 mellitus diabetes. The majority of patients were on insulin (42.92%).Ten (20.83%) were on oral hypoglycemic agents (OHA), and eleven patients (22.92%) were on combined insulin and OHA. Hypertension was found in 50% of diabetic patients. Mean duration of hypertension was 11±10years. Metabolic syndrome was found in 80%. The mean GFR (Glomerular Filtration Rate) in diabetic patients according MDRD equation was 69±41 ml/min/1.73m2. There were 44 patients (92%) with chronic renal disease ,with mean of BMI 26±5 kg/m2, mean of diastolic pressure 73±10 mmHg, mean of systolic pressure 125±18 mmHg , mean of Haemoglobin was10±2 g/dl, mean of fasting blood glucose 1.71±0.79g/l, mean of post prandial blood glucose 2.47±0.77g/l, mean of HBA1C 9±3%, mean of creatinine was 19±22 mg/l, mean of creatinine clearance was 69±41 ml/min/1.73m2. There was 32% with CKD1, 27% with CKD2, 14% with CKD4, 9% with CKD3A, 9% with CKD3B, and 9% with CKD5 stage of renal failure. Mean of HBA1C was 9±4 % in patients with CKD1, and patients in CKD5 with a mean HBA1C 13±2. Discussion: Kidney disease is far more common in people with diabetes than in people without diabetes. Diabetes is one of the leading causes of chronic kidney disease (CKD). Diabetes, hypertension and kidney failure are highly interlinked. On the one hand, type 2 diabetes is a leading cause of kidney failure, which is a risk for hypertension, and on the other, hypertension can often precede CKD and contribute to the progression of kidney disease. Both diabetes and CKD are strongly associated with cardiovascular disease (CVD) and therefore, the major component in their management is control of CVD risk factors such as hypertension and high blood glucose (hyperglycaemia). In our study population, advanced age was found. They were older, with overweight, and had a longer diabetes and hypertension duration. Diabetic with CKD patients also had a poor glycemic control. This strongly calls for effective screening for diabetic population at risk.

Tubular cell plasticity—new hope for autosomal dominant polycystic kidney disease?

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of chronic kidney disease. Typical forms of ADPKD are caused by mutations in either PKD1 or PKD2, encoding polycystin (PC)-1 and PC2, respectively. The polycystins are expressed in various membrane domains, including the primary cilium, and they play multiple roles in tubular cell homeostasis. The kidney cysts observed in patients with ADPKD derive from 1% to 3% of the nephrons and may involve all tubular segments.

IDF21-0591 Trends in Prevalence of Chronic Kidney Disease and Treatment Goals in Diabetes among US Adults, 1999–2018

Background: Diabetes is the leading cause of chronic kidney disease (CKD), the latter affecting 50% of patients with type 2 diabetes in the United States (US). Understanding population-wide trends in the prevalence of CKD and treatment goals in diabetes is critical to planning public health approaches for the prevention and management of CKD in diabetes. Aim: To determine trends in the prevalence of CKD, its risk factors, and diabetes treatment goals among US adults with diabetes between 1999–2000 and 2017–2018. Method: Ten cycles of cross-sectional National Health and Nutrition Examination Survey (NHANES) data between 1999–2000 and 2017–2018 were included. The sample included adults aged 20 years or older who had self-reported diagnosed diabetes. CKD was defined based on urine albumin-to-creatinine ratio ≥30 mg/g or estimated-glomerular filtration rate (eGFR) <60 mL/min/1.73m2. Diabetes treatment goals included HbA1c <8.0% (HbA1c target), blood pressure <130/80 mmHg (BP target), and total cholesterol <240 mg/dL (TC target). We estimated age- and sex-standardized prevalence of CKD in diabetes by sociodemographic characteristics and diabetes treatment goals. Logistic regressions were used to explore the associations of risk factors with the prevalence of CKD. Results: Amongst 5,976 participants with diabetes eligible for this analysis (mean age, 62.1 years; 51.5% men), the estimated standardized prevalence of CKD in diabetes decreased from 48.3% (95% CI: 47.9%, 48.6%) in 1999–2000 to 46.4% (46.2%, 46.5%) in 2017–2018 (average annual percentage changes, AAPC=−0.9 [−1.8, 0.0]). The main decreasing in prevalence of CKD occurred in women (AAPC=−1.2 [−2.1, −0.3]). The prevalence of CKD was 41% and 51% among patients with and without achieving HbA1c target in 2017–2018. The respectively figures were 37% and 54% for BP target, 45% and 47% for TC target. The youngest patients (20–39 years) achieved diabetes treatment of HbA1c and BP targets had lowest prevalence of CKD. Association analysis suggested that patients with achieving targets of BP (adjusted odds ratio, OR= 0.86 [0.81, 0.91]), HbA1c (OR= 0.88 [0.82, 0.94]), and two or all three of treatment goals (OR=0.77 [0.66, 0.90] and OR=0.70 [0.60, 0.82]) were less likely present CKD. Discussion: Based on NHANES data from US adults, the estimated prevalence of CKD in diabetes decreased between 1999–2000 and 2017–2018. The young patients with diabetes had a low percentage of achieving diabetes treatment targets. The reduced risk association of achieving diabetes treatment targets with the prevalence of CKD was more robust among the young patients calls for targeted action.

Effects of Primary Kidney Disease Etiology on Renal Osteodystrophy in Pediatric Dialysis Patients.

ABSTRACTCongenital diseases of the kidney and urinary tract (CAKUT) and glomerulonephritis are the main causes of chronic kidney disease (CKD) in children. Although renal osteodystrophy (ROD) and indices of mineral metabolism have been characterized in dialyzed children, the impact of primary kidney disease on ROD is unknown. We performed a cross‐sectional study of bone biopsies performed in 189 pediatric dialysis patients aged 12.6 ± 5.4 years. Patients were classified into three groups according to primary kidney disease: CAKUT (n = 82), hereditary (n = 22), or glomerular disease (n = 85). Serum concentrations of calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 25(OH) vitamin D were measured at the time of biopsy. Fibroblast growth factor 23 (FGF23) levels were measured in a subset of 59 patients. Levels of calcium, phosphate, PTH, and 25(OH) vitamin D were similar across groups. CAKUT patients had higher serum ALP and lower C‐terminal FGF23 levels. Bone turnover and bone volume parameters did not differ across groups. However, osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid maturation time (OMT) were highest in the CAKUT group and lowest in the hereditary group. Multiple regression analysis revealed that calcium, phosphate, ALP, and PTH were independently associated with OV/BV and osteoid thickness (O.Th). PTH was an independent factor affecting bone formation rate. The relationship between CKD etiology and bone histomorphometric variables was abrogated after adjustment for biochemical parameters in the multivariable models. Overall, bone histology differed according to CKD etiology in the unadjusted analysis; however, this association could not be confirmed independently of biochemical parameters. Although CAKUT patients had a greater mineralization defect with elevated serum ALP levels, longitudinal studies will be needed to elucidate mediation pathways that might be involved in the complex interplay of CKD‐mineral bone disease (MBD). © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Assessment of APACHE II Score to Predict ICU Outcomes of Patients with AKI: A Single-center Experience from Haryana, North India.

BackgroundThe acute physiology and chronic health evaluation (APACHE) II severity score has shown a good calibration and discriminatory value across a range of disease processes and remains the most widely used source of prognostic information on the risk for death in patients admitted to intensive care units (ICUs).ObjectivesTo study APACHE II scores in patients of acute kidney injury (AKI) admitted in the ICU and to find its association with outcome.Materials and methodsOne hundred patients with AKI aged 18 years or above were admitted in the ICU, department of general medicine, of a tertiary care institute in Haryana, North India, from October 2019 to September 2020, were studied. Patients who had known causes of chronic kidney disease (CKD), on maintenance hemodialysis, and those who underwent renal replacement therapy (RRT) or nephrectomy were excluded. All required investigations were performed, and data were collected. The patients were followed till discharge or in-hospital mortality.ResultsThe mean age of the patients was 55.92 ± 18.18 years. Male–female ratio was 1.5:1. Thirty-five percent of the admitted patients had an in-hospital mortality. Sepsis (47%) was the most common cause of AKI, and 83% of the patients had underlying comorbid conditions. The mean APACHE II score of the expired patients on admission, i.e., 24.80 ± 13.65, was found to be significantly higher compared to the mean APACHE II score (17.25 ± 10.12) of the discharged patients (p-value <0.001). APACHE II score was found to have 57.14% sensitivity, 86.15% specificity, 69% PPV, 78.9% NPV, and 76% diagnostic accuracy to predict mortality among the AKI patients.ConclusionAPACHE II scoring system has a good discrimination and calibration when applied to ICU-admitted AKI patients and is a good predictor of prognosis in them.How to cite this articlePatel P, Gupta S, Patel H, Bashar MDA. Assessment of APACHE II Score to Predict ICU Outcomes of Patients with AKI: A Single-center Experience from Haryana, North India. Indian J Crit Care Med 2022;26(3):276–281.

Focus on Finerenone, a Non-Steroidal MRA in Diabetic Kidney Disease. What Physicians Should Know?

Diabetes mellitus is not only a global concern in recent times but also has become the most common cause of chronic kidney disease which has a great impact on life expectancy, development of cardiovascular diseases, allcause mortality, and morbidity. Despite the recent addition of SGLT2inhibitors along with ACEi and ARBs in the treatment armamentarium of diabetic kidney disease (DKD), there is still an unmet need to minimize the risk of progression to ESKD. Mineralocorticoid Receptor (MR) overactivation has proven to be a significant risk factor in CKD progression which has been targeted as a novel therapeutic modality. Finerenone as a non-steroidal MR Antagonist (MRA) has unique features of the mechanism of action in regards to inhibition of recruitment of transcriptional cofactors implicated in hypertrophic, proinflammatory, and profibrotic gene expression. Salient pharmacokinetic features like shorter half-life, insignificant drug-drug interactions, and not forming any major active metabolite have put the molecule far ahead of its other congener varieties. Pre-clinical and clinical studies have established the safety and efficacy of this molecule in the treatment of DKD. In spite of those results, issues like an appropriate time of initiation of the drug and clinical outcome as add-on therapy have to address on large-scale trial basis.

Ebselen ameliorates renal ischemia-reperfusion injury via enhancing autophagy in rats.

Renal ischemia-reperfusion (I/R) injury is one of the most common causes of chronic kidney disease (CKD). It brings unfavorable outcomes to the patients and leads to a considerable socioeconomic burden. The study of renal I/R injury is still one of the hot topics in the medical field. Ebselen is an organic selenide that attenuates I/R injury in various organs. However, its effect and related mechanism underlying renal I/R injury remains unclear. In this study, we established a rat model of renal I/R injury to study the preventive effect of ebselen on renal I/R injury and further explore the potential mechanism of its action. We found that ebselen pretreatment reduced renal dysfunction and tissue damage caused by renal I/R. In addition, ebselen enhanced autophagy and inhibited oxidative stress. Additionally, ebselen pretreatment activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The protective effect of ebselen was suppressed by autophagy inhibitor wortmannin. In conclusion, ebselen could ameliorate renal I/R injury, probably by enhancing autophagy, activating the Nrf2 signaling pathway, and reducing oxidative stress.

Role of Zinc in Diabetic Kidney Disease.

Diabetic Kidney Disease (DKD) represents the most common cause of Chronic Kidney Disease (CKD) in developed countries. Approximately 30% to 40% of diabetes mellitus (DM) subjects develop DKD, and its presence significantly increases the risk for morbidity and mortality. In this context, Zinc seems to have a potential role in kidney and body homeostasis in diabetic individuals as well as in patients at a high risk of developing this condition. This essential element has functions that may counteract diabetes-related risk factors and complications, which include stabilization of insulin hexamers and pancreatic insulin storage and improved glycemic control. In our review, we analyzed the current knowledge on the role of zinc in the management of renal impairment in course of DM. Several studies underline the critical role of zinc in reducing oxidative stress levels, which is considered the common denominator of the mechanisms responsible for the progression of kidney disease. Reaching and maintaining a proper serum zinc level could represent a valuable target to reduce symptoms related to DM complications and contrast the progression of kidney impairment in patients with the high risk of developing end-stage renal disease. In conclusion, analyzing the beneficial role of zinc in this review would advance our knowledge on the possible strategies of DM and DKD treatment.

Drug Testing for Chronic Kidney Disease and Diabetes in Animals versus Humans: A Comparative Analysis of Study Designs and Reporting Qualities

Introduction: Diabetes is a highly prevalent accelerator or even cause of chronic kidney disease imposing a large unmet medical need at the global scale. Massive research activities continue to be in search of a cure but the yield of the classical bench-to-bedside research approach has been low. We speculated that a significant mismatch in design and quality of animal and clinical studies in this domain is a hurdle for translation. Methods: We performed a meta-analysis of matched pairs of animal and human studies that tested the efficacy of distinct drug interventions for diabetic kidney disease (DKD). We reviewed study designs and reporting quality of such studies over the last decade according to the standards listed in the CONSORT and ARRIVE recommendations, respectively. Results: We noted a wide diversity in the study designs of animal studies in terms of diabetes induction. Major mismatches with the respective human studies referred to age and sex distribution, comorbidities, stage of the kidney disease, and selection of primary endpoints. Usually, treatment was initiated before onset of kidney disease without any standard of care as a background therapy. The reporting quality of animal studies was poor for randomization procedures, blinding, sample size calculation for a prespecified primary endpoint or the safety analysis. Reporting quality of clinical studies had deficits in trial design-, recruitment-, allocation-, and outcome-related aspects. Conclusion: Bench-to-bedside translation in the domain of DKD suffers from major deficits in the design of experimental studies in view of the projected clinical trials as well as from significant deficits in the reporting quality in preclinical and clinical studies.

Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study.

The Kidney Disease: Improving Global Outcomes guidelines advocate the cause-glomerular filtration rate (GFR)-albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction. We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n=778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n=1117, analysis B). In analysis A, adding biopsy-proven diagnoses to the GFR-albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine-Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11-15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09-13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02-8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05-17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24-0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39-0.97)]. The CGA classification is of greater value in predicting outcomes than the GA classification.

Recurrence of Nephrolithiasis and Surgical Events Are Associated with Chronic Kidney Disease in Adult Patients.

Background and objective: Nephrolithiasis (NL) is a public health problem in the population of Southeast Mexico because of its high prevalence and recurrence. The evolution of this pathology can result in renal damage and may even cause chronic kidney disease (CKD), leading to a reduced glomerular filtration rate (GFR), decreased kidney function, and kidney loss in advanced stages. However, few studies support this evidence in the population. The present study aimed to determine risk factors associated with CKD in adult patients in an endemic population of Mexico. Materials and methods: A case-control study was carried out with patients diagnosed with NL. Additionally, the clinical information of patients (age, weight, height, blood pressure, comorbidities, and time of progress of NL), characteristics of the stones (number, location, and Hounsfield units), and biochemical parameters were collected. Results: The recurrence of NL was associated with CKD (OR 1.91; 95% CI 1.37–2.27; p = 0.003). In addition, male sex (p = 0.016), surgical history (p = 0.011), bilateral kidney stones (p < 0.001), and urinary tract infections (p = 0.004) were other factors associated with CKD. Interestingly, thirty-two patients younger than 50 years old with >2 surgical events presented a significant decrease in GFR (p < 0.001). Conclusions: The recurrence of NL and the number of surgical events were risk factors associated with CKD in patients with NL treated in our population.