Advanced Stages Of Chronic Kidney Disease Research Articles

#1244 Rates of eGFR and UACR testing in patients with chronic kidney disease in England: Clinical Practice Research Datalink 2010-2019

Abstract Background and Aims The NICE chronic kidney disease (CKD) treatment guidelines recommend regular laboratory measurements of both kidney function (eGFR) and damage (proteinuria) to appropriately inform efforts to prevent and treat progression of CKD. Recommendations also indicate frequency of such testing should increase with CKD progression. There are few data on rates of testing in patients with confirmed CKD with particularly paucity in patients with various stages of CKD. Method This non-interventional, observational study utilised data from primary care electronic health records from Clinical Practice Research Datalink (CPRD) AURUM. Patients aged ≥18 years with CKD registered in CPRD with at least one year of follow-up (FU) between January 1, 2010 and December 31, 2019 were identified. CKD was defined by an eGFR <60 ml/min/1.73 m2 and/or presence of a uACR measurement ≥3 mg/mmol, both confirmed by a second measurement 90-365 days later (index). Patients with eGFR <9 ml/min/1.73 m2 at index were excluded. Frequency of renal testing (eGFR and UACR) for each complete year of FU was quantified starting the day after index and patients were censored the last day of the final complete calendar year of FU after index. Frequency of renal testing per FU year was calculated overall and by CKD stage and level of albuminuria at index. Results In the 650 565 patients with CKD identified, mean age (SD) was 76.1 (11.3) years, 55.4% were female, and 88.5% White. Most (62.0%) patients had stage 3a CKD (eGFR 45-<59 ml/min/1.73 m2) at index. Among patients with UACR measurements within 1 year prior to index (54.1%), 49.3% were A1 (<3 mg/mmol), 43.4% A2 (3-30 mg/mmol) and 7.3% A3 (>30 mg/mmol) at index. During the first year of FU, 81.45% of patients had 1+ eGFR test whereas 39.2% had 1+ UACR test. Patients more frequently received 1+ eGFR per year over subsequent years of FU but the low proportion with 1+ UACR test per year remained stable for UACR. The mean (SD) number of eGFR and UACR tests performed per patient in the first year of FU was 2.09 (2.39) and 0.49 (0.70), respectively. More frequent eGFR testing was observed with lower eGFR at index and across subsequent years of FU. Frequency of UACR testing was lower at more advanced stages of CKD at index in all FU years, however, no trends in UACR testing frequency were observed by level of albuminuria at index. Conclusion This evidence from a population-based sample of patients with confirmed CKD in England, indicates that eGFR is being monitored in the majority of patients, yet UACR testing is suboptimal according to NICE guidelines regardless of level of kidney function or level of albuminuria. Although eGFR testing is more frequent at more advanced stages of CKD, UACR testing seems to become less frequent with more advanced stages of CKD. With emergence of new therapies to prevent progression of CKD, efforts to increase frequency of UACR testing are needed (particularly in earlier CKD stages) to ensure that patients who are at risk of worsening CKD and albuminuria receive appropriate management.

#1968 IgA nephropathy and impact of proteinuria and kidney function decline on healthcare resource utilisation among adults in the United Kingdom

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and can result in kidney failure, especially if left untreated. Proteinuria ≥1.0 g/day is a major risk factor for IgAN progression and rapid kidney function decline. This study describes the characteristics of patients with IgAN in the United Kingdom (UK) and the impact of proteinuria and chronic kidney disease (CKD) stage on healthcare resource utilisation (HRU) and costs. Method In this retrospective, descriptive analysis, eligible patients had at least one code among ICD-9 583.9, ICD-10 N02.8, and ICD-10 N02.9 between 1 October 2015 and 1 October 2022. They were stratified by CKD stage and proteinuria level. CKD stage was defined by ICD-10 N18 code and estimated glomerular filtration rate. Proteinuria level was grouped as low or high by protein excretion rate (<1 g/day vs ≥1 g/day), protein/creatinine ratio (<0.88 g/g vs ≥0.88 g/g), or albumin/creatinine ratio (<100 mg/mmol vs ≥100 mg/mmol). HRU data for 1 year from the index date were obtained from electronic medical records, and costs were obtained from the National Schedule of the National Health Service 2021/22. Weighted average costs were calculated for inpatient, outpatient, and emergency visits. Results We identified 6 940 patients with IgAN. The mean age was 62 years, and most patients (n = 3 980; 57%) were male. For all visit types, HRU (Fig.) and costs (Table) increased with advancing CKD. For all visit types combined, the mean total cost per patient was >23 times higher for CKD stage 5 than stage 1 (£60 259 vs £2 609). Of 2 080 patients with proteinuria data, 560 (27%) had high proteinuria. Annual costs per patient (Table) and the numbers of all visit types (Figure) were higher for patients with a protein excretion rate ≥1 g/day than those with a rate <1 g/day (£12 622 vs £2 822). Conclusion In patients with IgAN in the UK, elevated proteinuria and advanced CKD stage were associated with higher HRU and costs across visit types. Treatments that reduce proteinuria can slow disease progression and prevent rapid decline in kidney function while potentially reducing IgAN-related resource utilisation and costs.

#1066 Unobvious long-term effects of COVID-19 for kidneys

Abstract Background and Aims The impact of COVID-19 on the chronic kidney disease (CKD) has already been confirmed by researchers around the world. However, there is still no description of this infection influence on kidney function without signs of CKD before it. Method The study included 359 patients from the Moscow region who applied to the nephrologist of the first level regional center in 2022, 154 men and 205 women, mean age 59±16 years. Among the patients who applied for the past year, there were 70 patients with a previously confirmed diagnosis of CKD and 289 who first applied to a nephrologist and had no nephrology complaints, clinical or laboratory signs of CKD before. Results A total of 95 patients from both groups had COVID-19 in 2020-2022 before a visit to a nephrologist, 45 people from the group with CKD (47.4%) and 50 people (52.6%) who were not diagnosed with CKD before COVID-19. 20.4% had COVID-19 earlier than 2 months ago, 6.4% - from 2 to 6 months ago, 45.3% - from 6 to 12 months ago, 27.9% from 12 to 24 months ago. A mild degree of COVID-19 was in 49.4% of patients, moderate - 43, 3%, heavy - 7.3%. It is important to note that 48 patients (96%) who first contacted a nephrologist after COVID-19 were diagnosed with CKD (CKD stages 1-2 - 14 patients (29.17%), 3A and 3B stages - 24 patients (50%), 4 and 5 stages - 10 patients (20.83%)). Relative risk of stage 3+ CKD after COVID-19: RR= 1.036 [95% CI 0.8961 to 1.170], p=0.6742, relative risk of stage 5 CKD: RR= 0.7164 [95% CI 0.3259 to 1.534], p= 0.5403. Thus, the development of advanced (3+) stages of CKD cannot be directly related to past COVID-19. However, if we consider the risk of developing advanced stages of CKD for patients who have experienced moderate to severe COVID-19, then the relative risk of stage 3+ CKD: RR= 1.082 [95% CI 0.8936 to 1.236], p= 0.4607, and relative risk of stage 5 CKD RR = 1.013 [95% CI 0.4134 to 2.341], p>0.9999. Conclusion Unfortunately, it is not possible to link the risk of developing CKD in patients after COVID-19 with the timing after COVID-19 at this stage of the study. In addition, the relationship between COVID-19 and CKD stage cannot be assessed without taking about the structure of CKD causes in both groups. Obviously, a larger and deeper study of this issue is needed, possibly with more patients and long-term monitoring of the dynamics of renal function in patients of both groups.

#2034 CKD-MBD management: results from a national survey on bone turnover biomarkers practice and therapeutic strategies among Italian nephrologists

Abstract Background and Aims Advanced stages of chronic kidney disease (CKD) are constantly characterized by a mineral and bone disorders (MBD) syndrome concerning a complex systemic condition that includes laboratory abnormalities of bone and mineral metabolism involving calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; abnormalities in bone turnover, mineralization, volume, or strength; extra-skeletal calcifications, such as vascular or other soft tissue. CKD-MBD syndrome determines relevant consequences in terms of fragility fractures, cardiovascular events and higher mortality. The nephrologist's awareness of CKD-MBD diagnostic and management tools and therapeutic strategies is key to improving CKD patients’ prognosis and outcomes. Method A new national survey (composed of 17 online questions) was conducted among Italian nephrologists to investigate the reference laboratory availability of bone turnover markers (BTMs), the clinical attitude on secondary hyperparathyroidism (sHPT) management, and the CKD-MBD therapeutic approach in different stages of CKD and dialysis patients. Results 89 Italian nephrologists participated in the survey. The reference laboratories largely fulfill the biomarkers request of ionized calcium (97.7%), phosphorus (100%), PTH (100%), alkaline phosphatase (ALP) (100%), magnesium (100%), 25-OH and 1,25-OH vitamin D levels (92.1%; 53.9%); while most of the hospital laboratories do not regularly support the availability of specific BTMs, both for diagnosis and monitoring the bone resorption and formation (Fig. 1)—such as bone ALP (75.3%), calcifediol (37.1%), calcitriol (40.5%), fibroblast growth factor-23 (FGF-23) (intact 9% and c-terminal 4.5%), vitamin K (33.7%), Klotho (6.75%, soluble 4.5%), osteocalcin (38.2%), matrix gla protein (10.1%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (6.75%), cross-linked collagen type I peptide (CTX) (32.6%) and procollagen type 1 n-terminal propeptide (P1NP) (10.1%). The nephrologist's attitude to start management and treatment of sHPT is revealed to be mainly led by KDOQI (n = 42, 47%) and KDIGO (n = 39, 44%) guidelines considering their PTH cut-off values; in 53.9% of clinicians the measure of PTH levels is then performed every 3 months according to KDOQI guidelines. In relation to the definition of high turnover metabolic bone disease by BTMs, this metabolic pattern is identified in > 50% and 30-40% of patients with CKD 4-5D by 31.5% and 21.4% of nephrologists, respectively. 65% of clinicians currently considered ALP of equal importance as alterations of PTH as a predictor of fracture events. Other biomarkers, such as FGF-23, P1NP or TRAP-5b, emerge to not be still used in regular clinical practice. In patients diagnosed with CKD-MBD and skeletal fragility, 76.4% of nephrologists consider the AIFA (Italian Medicines Agency) note 79 to support osteoporosis treatment. The therapeutic strategies of CKD-MBD include the administration of vitamin D (e.g. cholecalciferol 27-37.1%, calcifediol 9-12.4%, calcitriol 42.7-55.1%) and its analogues (e.g. paricalcitol 23.6-52.8%) and the use of antiresorptive agents (e.g. alendronate 3.4%-23.6%, denosumab 22.5%-30.3%) with variable frequencies among different advanced CKD stages and for those patients on peritoneal or hemodialysis (Fig. 2). Conclusion Results present a suboptimal use of BTMs and a current heterogeneous therapeutic management of CKD-MBD syndrome and renal osteodystrophy in Italian clinical practice. The survey represents a starting point of work to further implement awareness of diagnostic and therapeutic issues of CKD-MBD.

#612 Serum citrulline level is associated with oxidative stress and chronic kidney disease progression

Abstract Background and Aims Citrulline, an α-amino acid crucial for the urea cycle and nitric oxide production, plays a protective role against free radicals and is indirectly related to protein metabolism. It is synthesized in the intestine and efficiently absorbed by the proximal renal tubules, where it is converted to urea via arginine. Although citrulline has multiple physiological effects, its involvement in the progression of chronic kidney disease (CKD) has not been explored. This cross-sectional study aimed to investigate the relationship between serum citrulline levels, CKD progression, and markers of oxidative stress. Method A total of 135 subjects were enrolled in this cross-sectional study. This cohort included 30 relatively healthy individuals who constituted the control group and 105 CKD patients who were categorized according to their estimated glomerular filtration rate (eGFR). We measured serum citrulline concentrations along with markers of oxidative stress, including paraoxonase 1 (PON-1), myeloperoxidase (MPO), and malondialdehyde (MDA), using the spectrophotometric method. Data were expressed as mean (M) and standard deviation (SD) or median and interquartile range [Me (Q25-Q75)] according to the data distribution and compared with the Kruskal-Wallis test. Spearmen correlation test was performed to evaluate the correlation between the studied data. Results Our findings revealed a significant increase in citrulline and MDA concentrations and MPO activity and a significant decrease in PON-1 in the CKD group compared with the control group. Moreover, a significant association emerged between serum citrulline levels and the severity of CKD, as determined by eGFR. Specifically, patients in advanced CKD stages exhibited elevated serum citrulline concentrations in contrast to those in earlier stages (Table 1). Furthermore, a significant correlation was established between serum citrulline and oxidative stress markers, with higher citrulline levels positively associated with increased concentrations of MDA (r = 0.46, p = 0.002) and heightened MPO activity (r = 0.85, p < 0.001), and demonstrating an inverse relationship with PON-1 in CKD stages 1-2 and 5 (r = -0.64, p < 0.001 and r = -0.47, p = 0.004, respectively). Conclusion This cross-sectional study suggests that serum citrulline level is associated with both CKD progression and oxidative stress intensity in patients with CKD. These findings highlight the potential role of citrulline as a biomarker for CKD progression and its implications in the management of oxidative stress in CKD. Further research is warranted to elucidate the underlying mechanisms and explore the therapeutic potential of citrulline supplementation in CKD patients.

Clinical epidemiology of cardiovascular disease in advanced chronic kidney disease prior to dialysis to a tertiary care centre in Bangladesh

Background: Patients with advanced CKD stages exhibit a markedly elevated risk of cardiovascular disease. Patients with chronic kidney disease (CKD) exhibit an elevated cardiovascular risk manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death .The main objective of this study was to observe the clinical epidemiology of cardiovascular disease in advanced stages of CKD prior to dialysis to a tertiary care centre in Bangladesh. Methods: This was a cross-sectional observational study on 150 cases of diagnosed advanced stages (4&5) of CKD patients in the indoor Department of Medicine of Sir Salimullah Medical College Mitford Hospital, Dhaka, Bangladesh from July 2022to January2023 for 6 months. Data was analyzed SPSS 25. Results: Out of the total group, 62.0% are male, 38.0% are female, and the average (mean) age of the entire group was 55.2 ±10.3. Patients are compared in terms of their relative percentages and the associated cardiovascular disease (CVD) risk, with the hypothesis that lower hemoglobin levels (<9 mg/dL), common in advanced CKD, may be associated with higher CVD risk. A statistically significant P-value (0.036) indicates a significant association between lower hemoglobin levels and increased risk of CVD. Hypertension is the most common risk factor in both stages showing (80%) in stage 4 and 86.6% in Stage -5 of CKD respectively that increasing prevalence as stages of CKD increases . Other factors like diabetes 50.6%) and 53.3% , dyslipidemia 61.3% and 66.7% , and family history of cardiovascular disease (CVD) 40% and 46.6% also in prevalence from Stage 4 to Stage 5. However, the differences in the prevalence of these risk factors between the two stages are not statistically significant, as indicated by the P-values. The prevalence of Congestive Heart Failure rises from 44% in Stage 4 to 52% in Stage 5, and a similar trend is observed in Coronary Artery Disease from 40% in Stage 4 to 48% in Stage 5 and for other diseases, albeit with lesser increments. The provided pvalues, which assess statistical significance, indicate that the differences in disease prevalence between the two stages are not statistically significant, suggesting that the progression from Stage 4 to Stage 5. Conclusion: This study stated that increased prevalence and progression of cardiovascular risks in advanced CKD stages. Bangladesh J Medicine 2024; 35: 96-100

My Plate Awareness and Engagement and Perceived and Objective Diet Quality in US Adults with Chronic Kidney Disease

Awareness of federal dietary guidelines has been associated with better perceived and objective diet quality. Little is known about the awareness of federal dietary recommendations among persons with chronic kidney disease (CKD) and the associations between recognition of guidelines, perception of diet quality, and objective quality of the diet in this population. We compared awareness of, and engagement with, MyPlate (a representation of five food groups from the US Department of Agriculture) along with perceived and objective diet quality, the latter assessed via Dietary Approaches to Stop Hypertension (DASH) index scores, among US adults with and without CKD during 2017-2020. Among non-institutionalized adults in the US, 8.3% had albuminuria with normal or near normal kidney function, 4.0% had estimated glomerular filtration rate (eGFR) 45-59 mL/min/1.73m2 (CKD stage G3a) and 1.6% had eGFR <45 mL/min/1.73m2 (CKD stages G3b/G4/G5). MyPlate awareness was lower among persons with CKD compared with those without CKD (19.6% versus 26.4%, p<0.001) and was lower among persons with more advanced CKD stages: 20.8%, 18.2%, and 16.3% in persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend p<0.001). Among persons aware of MyPlate, a numerically higher proportion with CKD attempted to follow My Plate recommendations (43.9% versus 32.3%, p=0.10); the proportion was highest among persons with moderate-to-advanced CKD (41.9%, 42.9%, and 56.9% among persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend p<0.001). Perceived and objective dietary quality (the latter based on concordance with the Dietary Approaches to Stop Hypertension diet) were slightly higher among persons with CKD relative to those without CKD. Adults with CKD have lower MyPlate awareness than adults without CKD. Enhancing diet education to persons with CKD could improve diet quality and potentially ameliorate CKD-associated complications.

Zinc and Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) poses a major global public health challenge. The World Health Organization's data shows that CKD affects about 10% of the world's population, particularly in low- and middle-income countries. Due to limited access to diagnosis and treatment, CKD has become the 12th leading cause of death worldwide. The advanced stage of CKD can lead to kidney failure, which is clinically referred to as end-stage renal disease (ESRD). In such cases, patients can only sustain life through dialysis or kidney transplantation. However, the long-term affordability of these treatments remains low. Moreover, the effectiveness of kidney transplantation is modest, posing a significant treatment barrier in resource-limited settings, and significantly impacting patient survival. To address this issue, we suggest using dietary supplementation of the trace element zinc to impede CKD development and prolong patient survival.

Impact of Sex Differences on Clinical Outcomes in Patients Following Primary Revascularization for Acute Myocardial Infarction - Insights From the Japanese Nationwide Registry.

Women with acute myocardial infarction (AMI) often present a worse risk profile and experience a higher rate of in-hospital mortality than men. However, sex differences in post-discharge prognoses remain inadequately investigated. We examined the impact of sex on 1-year post-discharge outcomes in patients with AMI undergoing percutaneous coronary intervention.Methods and Results: We extracted patient-level data for the period January 2017-December 2018 from the J-PCI OUTCOME Registry, endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics. One-year all-cause and cardiovascular mortality and major adverse cardiovascular events were compared between men and women. In all, 29,856 AMI patients were studied, with 6,996 (23.4%) being women. Women were significantly older and had a higher prevalence of comorbidities than men. Crude all-cause mortality was significantly higher among women than men (7.5% vs. 5.4% [P<0.001] for ST-elevation myocardial infarction [STEMI]; 7.0% vs. 5.2% [P=0.006] for non-STEMI). These sex-related differences in post-discharge outcomes were attenuated after stratification by age. Multivariate analysis demonstrated an increase in all-cause mortality in both sexes with increasing age and advanced-stage chronic kidney disease (CKD). Within this nationwide cohort, women had worse clinical outcomes following AMI than men. However, these sex-related differences in outcomes diminished after adjusting for age. In addition, CKD was significantly associated with all-cause mortality in both sexes.

A Significance of Selective Inhibition of Urate Transporter 1 and Non-Inhibition of Adenosine Triphosphate-Binding Cassette Transporter in Renal Function in a Patient With Advanced Stage Chronic Kidney Disease

A Significance of Selective Inhibition of Urate Transporter 1 and Non-Inhibition of Adenosine Triphosphate-Binding Cassette Transporter in Renal Function in a Patient With Advanced Stage Chronic Kidney Disease

Integration of Urinary Peptidome and Fecal Microbiome to Explore Patient Clustering in Chronic Kidney Disease.

Millions of people worldwide currently suffer from chronic kidney disease (CKD), requiring kidney replacement therapy at the end stage. Endeavors to better understand CKD pathophysiology from an omics perspective have revealed major molecular players in several sample sources. Focusing on non-invasive sources, gut microbial communities appear to be disturbed in CKD, while numerous human urinary peptides are also dysregulated. Nevertheless, studies often focus on isolated omics techniques, thus potentially missing the complementary pathophysiological information that multidisciplinary approaches could provide. To this end, human urinary peptidome was analyzed and integrated with clinical and fecal microbiome (16S sequencing) data collected from 110 Non-CKD or CKD individuals (Early, Moderate, or Advanced CKD stage) that were not undergoing dialysis. Participants were visualized in a three-dimensional space using different combinations of clinical and molecular data. The most impactful clinical variables to discriminate patient groups in the reduced dataspace were, among others, serum urea, haemoglobin, total blood protein, urinary albumin, urinary erythrocytes, blood pressure, cholesterol measures, body mass index, Bristol stool score, and smoking; relevant variables were also microbial taxa, including Roseburia, Butyricicoccus, Flavonifractor, Burkholderiales, Holdemania, Synergistaceae, Enterorhabdus, and Senegalimassilia; urinary peptidome fragments were predominantly derived from proteins of collagen origin; among the non-collagen parental proteins were FXYD2, MGP, FGA, APOA1, and CD99. The urinary peptidome appeared to capture substantial variation in the CKD context. Integrating clinical and molecular data contributed to an improved cohort separation compared to clinical data alone, indicating, once again, the added value of this combined information in clinical practice.

Work disability and employment status among advanced chronic kidney disease patients.

Chronic kidney disease (CKD) is a major public health issue with significant socioeconomic impacts. In Malaysia, the prevalence of CKD in 2018 was 15%. Complications of CKD such as anaemia, mineral bone disease, and infections led to frequent hospitalizations resulting in work disability and unemployment. To date, there is no data of employment status of CKD patients in Malaysia. A cross-sectional study of patients with advanced CKD (stage 4 and 5 non-dialysis) treated in our centre. We interviewed those aged 18 to 60 years old who were selected based on random sampling of their employment status and associated factors. Work disabilities and quality of life were assessed using work productivity and activity impairment (WPAI-GH) questionnaire and kidney disease and quality of life (KDQOL-36) questionnaire. These questionnaires were assisted by the main investigators to aid participants in facilitating their response process. A total of 318 patients recruited, 53.5% were males, with a mean age of 49.0 ± 9.0 years old. The main cause of CKD was diabetes (67.0%) followed by hypertension (11.3%). Majority of them were obese (55.3%) with a mean body mass index of 28.81 ± 6.3 kg/m2. The mean household income was RM 4669.50 ± 3034.75 (USD1006.27 ± 653.99). The employment rate was 50% (n = 159). 86% of the unemployed patients were in B40 income category. Multiple Logistic Regression was performed on the significant factors affecting employment status showed one year increase in age increased 6.5% odds to be unemployed. Female and dyslipidaemia had 2.24- and 2.58-times higher odds respectively to be unemployed. Meanwhile, patients with tertiary level of education were 81% less odds to be unemployed. Patients with advanced CKD had a mean percentage of 24.35 ± 15.23 work impairment and 13.36 ± 32.34 mean percentages of face absenteeism due to the disease burden. Furthermore, patients who were unemployed had significant perceived symptoms and problem lists, effects, and burden of kidney disease (p<0.01) and showed poor mental and physical composites (p<0.01) as compared with those who were employed. The employment rate of advanced CKD patients was low with half of patients lost their jobs due to the disease burden and had poor mental and physical composites of quality of life. This raises the concern for financial support for long term renal replacement therapy.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Urinary Vacuolar Casts Are a Unique Type of Casts in Advanced Proteinuric Glomerulopathies.

Identification of casts by urinary sediment microscopy is a valuable diagnostic clinical tool for the evaluation of kidney disease. Vacuolar casts are an unrecognized unique type of casts characterized by the presence of non-polarizable, clear vesicles of various sizes contained within a cast matrix, different from lipid casts, erythrocyte casts, or any other casts. We aimed to gain better understanding of the clinical relevance of these casts by establishing a multinational collaborative group to search for cases in which vacuolar casts were identified. Leveraging an educational social media platform, we conducted a multinational observational study extracting cases of patients who presented with urinary vacuolar casts during evaluation for impaired kidney function. Parameters assessed included degree of proteinuria and kidney dysfunction, clinical and histopathological diagnosis, and severity of renal parenchymal scarring on biopsy. A control group of cases without vacuolar casts was included for comparison. Forty-six cases with urinary vacuolar casts were compiled from 6 countries. Nephrotic range proteinuria (82%), glomerular etiology (98%) and advanced chronic kidney disease stage (62% 3B-5) were salient features. Histopathological diagnosis was available in 26 (57%) cases. Combining clinical and pathological diagnoses, diabetic nephropathy (48%), arterionephrosclerosis (30%), podocytopathies (15%) and proliferative glomerulonephritides (15%) accounted for most cases. Vacuolization of tubules or podocytes was present in 61% of the specimens. When compared to cases with histopathological diagnoses in which vacuolar casts were not found (n=186), cases with vacuolar casts more frequently had a glomerular etiology (100% vs 71%, p=0.002), had greater proteinuria (median urine protein-to-creatinine 10.3 vs 2.2 g/g, p<0.001) and had greater proportion of patients with ≥ 30% glomerular obsolescence (46% vs 20%, p = 0.003). Thus, urinary vacuolar casts are strongly associated with advanced glomerulopathies with severe proteinuria. Future studies should examine their origin, composition, and prognostic value.

Exploring dyslipidemia and cardiovascular morbidity in chronic kidney disease patients: A cross-sectional study

ABSTRACT Introduction: Chronic kidney disease (CKD) is a prevalent health concern with significant implications for patient health. This study investigates the relationship between dyslipidemia and cardiovascular morbidity in CKD patients. CKD is characterized by kidney damage, reduced glomerular filtration rate, and is associated with various complications, including cardiovascular disease. Dyslipidemia, characterized by abnormal lipid levels, is common in CKD patients and contributes to the development of atherosclerosis and cardiovascular complications. Materials and Methods: This 1-year cross-sectional observational study was conducted at a tertiary care center in northern India. The study included 160 patients aged 16 and above who had been diagnosed with CKD. Researchers conducted a comprehensive analysis of lipid profiles in these patients and assessed cardiovascular morbidity through a review of clinical records. Results: In our study, we observed that 96 out of 160 patients diagnosed with CKD exhibited lower than recommended levels of high-density lipoprotein (HDL). Furthermore, in patients with CKD Stages IV and V, low-density lipoprotein (LDL) cholesterol (LDL-C) levels were notably elevated. Triglyceride levels (TGs) were consistently elevated across the board in our study. Specifically, the mean TGLs were 159, 162.8, 211, and 246.8 in CKD Stages II, III, IV, and V, respectively, which was statistically significant. In addition, total cholesterol levels were found to be elevated in 110 out of 160 patients within our study group. Most of the patients with CKD were found to have systolic or diastolic dysfunction on two-dimensional echocardiography. Furthermore, associated coronary artery disease was higher in Grade III and Grade V CKD patients. The study yielded several notable findings regarding cardiovascular morbidity in CKD patients. Cardiovascular morbidity was observed in a significant proportion of CKD patients, highlighting the strong link between CKD and heart-related complications. Abnormal lipid profiles, such as low levels of HDL and elevated levels of LDL-C, were prevalent in CKD patients with cardiovascular morbidity. An association between the severity of CKD, as determined by Stage, and the presence of cardiovascular morbidity was evident. Patients with advanced CKD Stages (IV and V) were more likely to exhibit cardiovascular complications. Dyslipidemia, particularly elevated TGLs, was implicated as a potential contributor to cardiovascular morbidity in CKD patients. Conclusion: This study underscores the significance of cardiovascular morbidity in CKD patients and its association with dyslipidemia. Findings suggest that early diagnosis and management of dyslipidemia are essential for mitigating the long-term cardiovascular consequences in CKD patients. Health-care providers should be vigilant in monitoring lipid profiles in CKD patients and implementing appropriate interventions to reduce their risk of cardiovascular complications. By integrating the study’s findings on cardiovascular morbidity with dyslipidemia in CKD patients, health-care practitioners can better understand the multifaceted nature of this condition and tailor their treatment strategies accordingly.

Vitamin D Levels among Chronic Kidney Disease Patients at a Tertiary Care Hospital: A Cross-sectional Study

Introduction: In patients with Chronic Kidney Disease (CKD), a high prevalence of metabolite abnormalities has been observed. Numerous studies have demonstrated that individuals with reduced Glomerular Filtration Rate (GFR) are more susceptible to severe vitamin D deficiency compared to those with normal kidney function. Aim: To investigate the association between vitamin D levels and the severity of CKD among patients at Siddhartha Medical College, GGH in Vijayawada, Andhra Pradesh, India. Materials and Methods: The present hospital-based cross- sectional study was conducted at Siddhartha Medical College, GGH, Vijayawada, Andhra Pradesh, India from December 2021 to February 2022. A total of 100 CKD patients with a GFR of less than 60 mL/min/1.72 m2 were included in the study. Vitamin D levels were assessed using Chemiluminescence immunoassay (Access 2, Beckman Coulter), and vitamin D deficiency was defined as 25-OH vitamin D levels of less than 10 ng/mL, while insufficiency was defined as levels between 10 to 30 ng/mL. Statistical analysis was performed using Analysis of Variance (ANOVA) test and Pearson’s correlation test. Results: The mean age of the study population was 53.25±7.6 years, with the majority (32%) belonging to the 51-60 years age group. In terms of gender distribution, approximately three-fourths (72%) of the subjects were male. Hypertension was present in 44% of CKD patients, diabetes in 38%, and cardiovascular disease in 38%. Total 53% of CKD patients were classified as stage 4 on the Kidney Disease: Improving Global Outcome (KDIGO) CKD staging. Vitamin D deficiency was observed in 26% of patients, while 39% had insufficiency. A statistically significant association was found between the severity of CKD staging and mean vitamin D levels, with lower mean levels observed in stages 4 and 5. Conclusion: Vitamin D deficiency was present in one-fourth of the CKD patients, and it was more pronounced in advanced stages of CKD.

Quantifying carotid stiffness in chronic kidney disease using ultrafast ultrasound imaging.

The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.

Study of CD4+ T-lymphocytes in chronic kidney disease patients with COVID-19 infection

Chronic kidney disease (CKD) is a functional and/or structural kidney damage that lasts more than three months duration. This study aimed to analyze CD4+ T-lymphocytes levels in chronic CKD patients specifically, during the coronavirus disease 2019 (COVID-19) pandemic to assess the adaptive cell-mediated immunity. The study measured absolute CD4+ T-lymphocytes counts by flowcytometry among participating individuals. The study included 146 subjects, 40 CKD patients and tested positive for COVID-19, 44 CKD patients and tested negative for COVID-19 and 62 normal individuals as controls. There was a significant impact of COVID-19 infection in CKD patients showing lower absolute CD4+ T-lymphocytes values to more than six folds compared to the control individuals (Odds Ratio: 72.63, p= 0.0001). Also, there was a significant correlation between the decrease in absolute CD4+ T-lymphocytes counts and the advanced stages of CKD. Therefore, the study indicated that CKD causes an obvious alteration in the body immune system as decreased CD4+ T-lymphocytes levels alongside with the advanced CKD stages. While COVID-19 infection exposes CKD patients to be 50% more likely to express lower values of CD4+ T-lymphocytes levels compared to the negative tested CKD patients. In conclusion, poor immune response and increased morbidity and mortality could be correlated with CKD patients especially when associated with COVID-19 infection as comorbidity.

Sodium-Glucose Cotransporter-2 Inhibitors Utilization and Outcomes in Patients with Chronic Kidney Disease at a Tertiary Centre

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is an antidiabetic agent with cardiac and renal protective properties. Its renal protective property is a result of the inhibition of tubular sodium reabsorption and reduction in the intraglomerular pressure. The use of SGLT2 inhibitor in chronic kidney disease (CKD) independent of diabetic status is emerging. However, the real-world data of SGLT2 inhibitor utilisation in CKD is limited. We conducted a descriptive study of patients with CKD, who were prescribed with SGLT2 inhibitor in our Nephrology Clinic. A total of 156 patients were initiated on SGLT2 inhibitor from 2017 to 2022. Among them, 58.3% were male, with a mean age of 61 + 13 years, and 86.5% had diabetes mellitus, with estimated mean glomerular filtration rate (eGFR) of 46.41 + 21.14 ml/min/1.73m2, and proteinuria of 2.22 + 2.62 g/day. A total of 85.9% of patients were on renin-angiotensin-system (RAS) blockers, whereby those who were not prescribed with RAS were mostly CKD stage 4. Among the non-diabetic patients, 81% had glomerulonephritis, half of which was IgA nephropathy, and 42.9% were on immunosuppressants. There was a significant retardation of eGFR decline over a six-month-duration after the initiation of SGLT2 inhibitor from -3.46 + 6.56 ml/min/1.73m2 to -0.77 + 7.97 ml/min/1.73m2 (p=0.001). The retardation of eGFR decline was more pronounced in more advanced CKD stages. However, the proteinuria reduction was insignificant over a six-month-duration (-0.03 + 2.31 g/day). There were no adverse events reported. In conclusion, SGLT2 inhibitor retarded the eGFR decline with minimal proteinuria reduction in short-term. Nonetheless, long-term efficacy and safety data of SGLT2 inhibitor in local populations requires further evaluation.

Comparative effectiveness of first-line antihypertensive drug classes on the maintenance of estimated glomerular filtration rate (eGFR) in real world primary care

Renin-angiotensin system inhibitors (RASi), particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and are recommended for kidney protection. Uncertainty remains about the effectiveness of RASi being used as first-line antihypertensive therapy on eGFR maintenance compared to its alternatives, especially for those with no or early-stage chronic kidney disease (CKD). We conducted a retrospective cohort study of 19,499 individuals (mean age 64.1, 43.5% males) from primary care in Singapore with 4.5 median follow-up years. The study cohort included newly diagnosed individuals with hypertension (whose eGFR was mainly in CKD stages G1-G2) and initiated on ACEIs, ARBs, beta-blockers (BBs), calcium channel blockers (CCBs) or diuretics (Ds) as first-line antihypertensive monotherapy. We compared the estimated glomerular filtration rate (eGFR) curve before/after the drug initiation over time of patients under different drug classes and analyzed the time to declining to a more advanced stage CKD. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounding factors. Two key findings were observed. First, after initiating antihypertensive drugs, the eGFR almost maintained the same as the baseline in the first follow-up year, compared with dropping 3 mL/min/1.73 m2 per year before drug initiation. Second, ARBs were observed to be slightly inferior to ACEIs (HR = 1.14, 95% CI = (1.04, 1.23)) and other antihypertensive agents (HR = 1.10, 95% CI = (1.01, 1.20)) in delaying eGFR decline to a more advanced CKD stage in the study population. Our results showed that initiating antihypertensive agents can significantly maintain eGFR for those newly diagnosed patients with hypertension. However, RASi may not be superior to other antihypertensive agents in maintaining eGFR levels for non-CKD or early stages CKD patients.