Interventions for preventing haemodialysis dysequilibrium syndrome.

BACKGROUND: Dialysis dysequilibrium syndrome (DDS) refers to neurological symptoms usually seen during or after new initiation or following reinitiation of haemodialysis (HD) after missing multiple sessions. DDS is associated with death and morbidity. We studied interventions aimed at preventing DDS. OBJECTIVES: To evaluate the benefits and harms of different types of interventions for preventing DDS. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 8 May 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any intervention against standard care, including individuals initiated on HD, regardless of age. DATA COLLECTION AND ANALYSIS: Two authors independently determined study eligibility, assessed quality and extracted data. Data were collected on methods, interventions, participants, and outcomes (DDS incidence, severe DDS, death, adverse events). Risk ratios (RR) and confidence intervals (CI) were calculated. Study quality was assessed using the Cochrane Risk of Bias 2 (ROB2) tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included two RCTs, enrolling 32 adult participants. Interventions included were slow dialysis, sodium modelling, standard sodium dialysate, and high sodium dialysate. The risk of bias was of some concern to high risk of bias in both studies. Slow dialysis compared to sodium modelling (1 study, 15 participants) may result in little to no difference in DDS, severe DDS, and death (low certainty evidence) and has uncertain effects on adverse events (RR 1.33, 95% CI 0.15 to 11.64; very low certainty evidence). Standard sodium dialysate compared to high sodium dialysate (1 study, 17 participants) has uncertain effects on the incidence of DDS (RR 0.07, 95% CI 0.00 to 1.12), severe DDS (RR 0.47, 95% CI 0.02 to 10.32), and adverse events (RR 0.29, 95% CI 0.08 to 1.02) (very low certainty evidence). AUTHORS' CONCLUSIONS: In HD patients, sodium modelling, compared to slow dialysis, may result in little to no difference in DDS and death (low certainty evidence) and has uncertain effects on adverse events (very low certainty evidence). The evidence is very uncertain for the effect of high-sodium dialysate and standard sodium dialysate on DDS, death and adverse events (very low certainty evidence).

Ocular and systemic vascular endothelial growth factor ligand inhibitor use and nephrotoxicity: an update.

Tumor growth is intricately linked to the process of angiogenesis, with a key role played by vascular endothelial growth factor (VEGF) and its associated signaling pathways. Notably, these pathways also play a pivotal "housekeeping" role in renal physiology. Over the past decade, the utilization of VEGF signaling inhibitors has seen a substantial rise in the treatment of diverse solid organ tumors, diabetic retinopathy, age-related macular degeneration, and various ocular diseases. However, this increased use of such agents has led to a higher frequency of encountering renal adverse effects in clinical practice. This review comprehensively addresses the incidence, pathophysiological mechanisms, and current evidence concerning renal adverse events associated with systemic and intravitreal antiangiogenic therapies targeting VEGF-A and its receptors (VEGFR) and their associated signaling pathways. Additionally, we briefly explore strategies for mitigating potential risks linked to the use of these agents and effectively managing various renal adverse events, including but not limited to hypertension, proteinuria, renal dysfunction, and electrolyte imbalances.

Role of novel biomarker monocyte chemo-attractant protein-1 in early diagnosis & predicting progression of diabetic kidney disease: A comprehensive review.

Diabetic kidney disease (DKD) is the most devastating complication of diabetes mellitus. Identification of patients at the early stages of progression may reduce the disease burden. The limitation of conventional markers such as serum creatinine and proteinuria intensify the need for novel biomarkers. The traditional paradigm of DKD pathogenesis has expanded to the activation of the immune system and inflammatory pathways. Monocyte chemo-attractant protein-1 (MCP-1) is extensively studied, as a key inflammatory mediator that modulates the development of DKD. Recent evidence supports the diagnostic role of MCP-1 in patients with or without proteinuria in DKD, as well as a significant role in the early prediction and risk stratification of DKD. In this review, we will summarize and update present evidence for MCP-1 for diagnostic ability and predicting the progression of DKD.

Study of prevalence, clinical profile, and predictors of rapid progression in diabetic kidney disease.

BACKGROUND: A significant proportion of diabetic kidney disease (DKD) experience a rapid decline in eGFR, leading to end-stage kidney disease (ESKD) within months. This single-centered retrospective cohort study aimed to assess the prevalence, clinical profile, and predictors for rapid progression in type 2 diabetes mellitus (T2DM) patients with DKD. METHOD: Three hundred fifty-nine T2DM patients with DKD between January 2018 and 2022 were included and those with superimposed non-diabetic kidney disease, chronic kidney disease 5, and < 6 months follow-up were excluded. They were classified as rapid and non-rapid progressors based on the annual eGFR decline of > 5 ml/min/1.73 m2/year. The primary outcome analyzed was the progression to ESKD. The secondary outcomes were the onset of microvascular and macrovascular complications and predictors for rapid progression as well as ESKD. RESULTS: In a median follow-up of 3.5 years, 61.3% were rapid progressors (mean eGFR decline of 15.4 ml/1.73m2/year) and 38.7% were non-rapid progressors (mean eGFR decline 1.8 ml/1.73m2/year. Among rapid progressors, 61.4% reached ESKD. Severe proteinuria, the presence of retinopathy, and acute kidney injury (AKI) episodes were strong predictors of rapid progression. Cardiovascular disease and diabetic retinopathy (microvascular complications) were significantly higher among rapid progressors and had a mortality rate of 7.2%. CONCLUSION: The majority of type 2 DKD patients were rapid progressors and two-thirds of them developed ESKD. The prevalence of hypertension, cardiovascular disease, diabetic retinopathy, AKI episodes, and mortality was higher in rapid progressors. Severe proteinuria and diabetic retinopathy were found to be strong predictors for rapid eGFR decline and its progression to ESKD.

Hydroxychloroquine in nephrology: current status and future directions.

Hydroxychloroquine is one of the oldest disease-modifying anti-rheumatic drugs in clinical use. The drug interferes with lysosomal activity and antigen presentation, inhibits autophagy, and decreases transcription of pro-inflammatory cytokines. Owing to its immunomodulatory, anti-inflammatory, anti-thrombotic effect, hydroxychloroquine has been an integral part of therapy for systemic lupus erythematosus and lupus nephritis for several decades. The therapeutic versatility of hydroxychloroquine has led to repurposing it for other clinical conditions, with recent studies showing reduction in proteinuria in IgA nephropathy. Research is also underway to investigate the efficacy of hydroxychloroquine in primary membranous nephropathy, Alport's syndrome, systemic vasculitis, anti-GBM disease, acute kidney injury and for cardiovascular risk reduction in chronic kidney disease. Hydroxychloroquine is well-tolerated, inexpensive, and widely available and therefore, should its indications expand in the future, it would certainly be welcomed. However, clinicians should be aware of the risk of irreversible and progressive retinal toxicity and rarely, cardiomyopathy. Monitoring hydroxychloroquine levels in blood appears to be a promising tool to evaluate compliance, individualize the dose and reduce the risk of retinal toxicity, although this is not yet standard clinical practice. In this review, we discuss the existing knowledge regarding the mechanism of action of hydroxychloroquine, its utility in lupus nephritis and other kidney diseases, the main adverse effects and the evidence gaps that need to be addressed in future research. Created with Biorender.com. HCQ, hydroxychloroquine; GBM, glomerular basement membrane; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; TLR, toll-like receptor.

Chronic kidney disease of unknown aetiology: A comprehensive review of a global public health problem.

The term chronic kidney disease of unknown aetiology (CKDu) refers to chronic kidney disease (CKD) in the absence of diabetes, long-standing hypertension, glomerulonephritis, obstructive uropathy or other apparent causes. An increasing number of CKDu cases have been reported from Latin America, Sri Lanka, India and others over the last two decades. These regional nephropathies share the following common attributes: (a) they affect low-to-middle income countries with tropical climates, (b) involve predominantly rural agricultural communities, (c) male predilection, (d) absence of significant proteinuria and hypertension, and (e) chronic tubulointerstitial nephritis on kidney biopsy. The current body of literature suggests that CKDu may be caused by heat stress, agrochemicals, contaminated drinking water or heavy metals; however, considerable regional disparities in CKDu research make it difficult to establish a common causal link. In the absence of a definite aetiology, specific preventive and therapeutic interventions are lacking. Improvement of working conditions of farmers and labourers, provision of safe drinking water and changes in agricultural practices are some of the measures that have been implemented; however, there is lack of data to assess their impact on the incidence and progression of CKDu. There is a need for a concerted global effort to address the current knowledge gaps, and to develop effective and sustainable strategies to tackle this devastating disease.

Kannada Translation and Validation of the ESAS-r Renal for Symptom Burden Survey in Patients with End-Stage Kidney Disease.

Objectives: End-stage kidney disease (ESKD) is a life-limiting illness that leads to significant health-related suffering for the patients and their caregivers. Moreover, disease-directed options such as dialysis and renal transplant might not be universally accessible. Inadequate assessment and management of symptoms often lead to diminished quality of life. For evaluating symptoms and their associated distress, various tools have been identified. However, these are not available for the native Kannada-speaking population for assessing ESKD symptom burden. In this study, we determined the reliability and validity of the Edmonton Symptom Assessment System Revised Renal (ESAS-r: Renal) in Kannada-speaking ESKD patients. Materials and Methods: ESAS-r: Renal English version was translated into Kannada using the forward and backward method. The translated version was endorsed by Nephrology, Palliative care, Dialysis technology and Nursing experts. As a pilot study, 12 ESKD patients evaluated the content of the questionnaires for appropriateness and relevance. The ESAS-r: Renal Kannada version was validated by administering this tool to 45 patients twice a fortnight. Result: The translated ESAS-r: Renal Kannada version questionnaire had an acceptable face and content validity. Experts' opinion was assessed by content validity ratio (CVR), and the value of CVR of ESAS-r: Renal Kannada version was-'1'-. Internal consistency of the tool was assessed among Kannada-speaking ESKD patients; its Cronbach's α was 0.785, and test-retest validity was 0.896. Conclusion: The validated Kannada version of ESAS-r: Renal was reliable and valid for assessing symptom burden in ESKD patients.

Uremic pruritus: prevalence, determinants, and its impact on health-related quality of life and sleep in Indian patients undergoing hemodialysis.

BACKGROUND: Uremic pruritus has an impact on the quality of life and sleep of hemodialysis patients, but the majority of cases go unreported and untreated unless severe, due to a lack of awareness. The purpose of this study is to determine the prevalence, associated factors, and impact on health-related quality of life (HR-QOL) and sleep in hemodialysis patients. METHODOLOGY: A single-center observational study of 3 months wherein 120 adults on maintenance hemodialysis were included. Baseline characteristics, dialysis-related factors, and lab parameters influencing uremic pruritus were recorded. Those with uremic pruritus completed "12-item pruritus severity scale (12-PSS)", "SKINDEX10", and "Itch-MOS" questionnaires to evaluate severity, impact on HR-QOL, and sleep respectively. RESULTS: Sixty seven over one hundred twenty (55.83%) patients had pruritus and majority were mild (40.83%) as per 12-PSS. Those with pruritus (n=67) had a mean age of 56.5±11.3 years, most were males (82%), chronic glomerulonephritis (29.1%) was the commonest cause of end-stage kidney disease, 3 active smokers, and 4 seropositive. 65(97%) patients were on twice-weekly dialysis, 36/67 had <5 years' dialysis vintage and acceptable adequacy. There was no significant association between uremic pruritus and dialysis-related/laboratory parameters. Patients with uremic pruritus demonstrated significantly worse "HR-QOL" (p<0.001) on the "SKINDEX-10", and patients' "Itch-MOS" scores demonstrated a significant decline in sleep quality with increasing pruritus severity (p<0.001). CONCLUSION: The majority of patients on maintenance hemodialysis experience uremic pruritus. None of the clinical characteristics, dialysis-related factors, and laboratory parameters affected uremic pruritus. Uremic pruritus patients had the worst HR-QOL & their sleep quality significantly declined as pruritus severity escalated. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Study approval was obtained from Institutional Research Committee and Institutional Ethical Committee (IEC 642/2021). Clinical Trial Registry of India (CTRI) registration (CTRI/2022/01/039143) was also obtained.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

BACKGROUND: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, may increase the risk of death, and impacts kidney transplant outcomes. Direct-acting antivirals have replaced interferons because of better efficacy and tolerability. This is an update of a review first published in 2015. OBJECTIVES: We aimed to look at the benefits and harms of interventions for HCV in CKD patients on dialysis: death, disease relapse, treatment response/discontinuation, time to recovery, quality of life (QoL), cost-effectiveness, and adverse events. We aimed to study comparisons of available interventions, compared with placebo, control, with each other and with newer treatments. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 23 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register Portal (ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Three studies were included in this update, therefore 13 studies (997 randomised participants) met our inclusion criteria. Overall, the risk of bias was judged low in seven studies, unclear in four, low to unclear in one, and high in one study. Interventions included standard interferon, pegylated (PEG) interferon, standard or PEG interferon plus ribavirin; direct-acting antivirals, and direct-acting antivirals plus PEG interferon plus ribavirin. Compared to placebo or control, standard interferon may make little or no difference to death (5 studies, 134 participants: RR 0.89, 95% CI 0.06 to 13.23) or relapse (low certainty evidence), probably improves end-of-treatment response (ETR) (5 studies, 132 participants: RR 8.62, 95% CI 3.03 to 24.55; I² = 0%) (moderate certainty evidence), and probably makes little or no difference to sustained virological response (SVR) (4 studies, 98 participants: RR 3.25, 95% CI 0.81 to 13.07; I² = 53%), treatment discontinuation (4 studies, 116 participants: RR 4.59, 95% CI 0.49 to 42.69; I² = 63%), and adverse events (5 studies, 143 participants: RR 3.56, 95% CI 0.98 to 13.01; I² = 25%) (moderate certainty evidence). In low certainty evidence, PEG interferon (1 study, 50 participants) may improve ETR (RR 1.53, 95% CI 1.09 to 2.15) but may make little or no difference to death (RR 0.33, 95% CI 0.01 to 7.81), SVR (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96), adverse events (RR 0.11, 95% CI 0.01 to 1.96) and relapses (21/38 relapsed) (RR 0.72, 95% CI 0.41 to 1.25) compared to standard interferon. In moderate certainty evidence, high-dose PEG interferon (alpha-2a and alpha-2b) may make little or no difference to death (2 studies, 97 participants: RR 4.30, 95% CI 0.76 to 24.33; I² = 0%), ETR (RR 1.42, 95% CI 0.51 to 3.90; I² = 20%), SVR (RR 1.19, 95% CI 0.68 to 2.07; I² = 0%), treatment discontinuation (RR 1.20, 95% CI 0.63 to 2.28; I² = 0%) or adverse events (RR 1.05, 95% CI 0.61 to 1.83; I² = 27%) compared to low-dose PEG interferon. High-dose PEG interferon may make little or no difference to relapses (1 study, 43 participants: RR 1.11, 95% CI 0.45 to 2.77; low certainty evidence). There were no significant subgroup differences. Standard interferon plus ribavirin may lead to higher treatment discontinuation (1 study, 52 participants: RR 2.97, 95% CI 1.19 to 7.36; low certainty evidence) compared to standard interferon alone.  In low certainty evidence, PEG interferon plus ribavirin (1 study, 377 participants) may improve SVR (RR 1.80, 95% CI 1.46 to 2.21), reduce relapses (RR 0.33, 95% CI 0.23 to 0.48), slightly increase the number with adverse events (RR 1.10, 95% CI 1.01 to 1.19), and may make little or no difference to ETR (RR 1.01, 95% CI 0.94 to 1.09) compared to PEG interferon alone. The evidence is very uncertain about the effect of PEG interferon plus ribavirin on treatment discontinuation (RR 1.71, 95% CI 0.69 to 4.24) compared to PEG interferon alone. One study reported grazoprevir plus elbasvir improved ETR (173 participants: RR 174.99, 95% CI 11.03 to 2775.78; low certainty evidence) compared to placebo. It is uncertain whether telaprevir plus ribavirin (high versus low initial dose) plus PEG interferon for 24 versus 48 weeks (1 study, 35 participants) improves ETR (RR 1.02, 95% CI 0.67 to 1.56) or SVR (RR 1.02, 95% CI 0.67 to 1.56) because the certainty of the evidence is very low.  Data on QoL, cost-effectiveness, cardiovascular outcomes and peritoneal dialysis were not available. AUTHORS' CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.

A comparative analysis of conventional and speckle-tracking strain echocardiographic findings in diabetic and non-diabetic kidney disease patients with normal ejection fraction.

This study aimed to compare the differences in echocardiographic and strain parameters in patients with diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) in a cohort with pre-dialysis chronic kidney disease (CKD) and normal ejection fraction (EF). In this single-center prospective study, patients with CKD stages 3-5 and EF > 55% were included. We compared cardiac structure and function using conventional and speckle-tracking strain echocardiography among DKD and NDKD groups. Cardiovascular outcomes were assessed at the end of the study. Of the included 117 patients, 56 (47.9%) had DKD, and 61 (52.1%) had NDKD. Patients with DKD had higher ratios of early mitral inflow velocity and mitral annular early diastolic velocity (E/e') (11.9 ± 4.4 vs. 9.8 ± 3.5; p = 0.004), lower septal e' velocity (7.1 ± 2.5 vs. 8.2 ± 2.8; p = 0.031), lower lateral e' velocity (9.2 ± 2.9 vs. 10.4 ± 3.8; p = 0.045) and longer deceleration times (209.2 ± 41.5 vs. 189.1 ± 48.0; p = 0.017), compared to those with NDKD. Left ventricular mass index (LVMI), global longitudinal strain (GLS), early diastolic strain rate (SRE), and E/SRE were similar. At a median follow-up of 239 days, 3-P MACE (11.5% vs. 4.9%; p = 0.047) and 4-P MACE (28.6% vs. 11.5%; p = 0.020) were observed to be higher in the DKD group. Diastolic dysfunction was more common in patients with DKD, compared to those with NDKD, although both groups had similar LVMI and GLS. Those with DKD also had poorer cardiovascular outcomes. This highlights the importance of the assessment of diastolic function in CKD, particularly in those with diabetic CKD.

Novel biomarkers for prognosticating diabetic kidney disease progression.

The global burden of diabetic kidney disease (DKD) is escalating, and it remains as a predominant cause of the end-stage renal disease (ESRD). DKD is associated with increased cardiovascular disease and morbidity in all types of diabetes. Prediction of progression with albuminuria and eGFR is challenging in DKD, especially in non-proteinuric DKD patients. The pathogenesis of DKD is multifactorial characterized by injury to all components of the nephron, whereas albuminuria is an indicator of only glomerular injury. The limits in the diagnostic and prognostic value of urine albumin demonstrate the need for alternative and clinically significant early biomarkers, allowing more targeted and effective diabetic treatment, to reduce the burden of DKD and ESRD. Identification of biomarkers, based on multifactorial pathogenesis of DKD can be the crucial paradigm in the treatment algorithm of DKD patients. This review focuses on the potential biomarkers linked to DKD pathogenesis, particularly with the hope of broadening the diagnostic window to identify patients with different stages of DKD progression.

Hyponatremia in Melioidosis: Analysis of 10-year Data from a Hospital-Based Registry.

Introduction: Hyponatremia is a frequent finding in hospitalized patients and is associated with poor clinical outcomes. While hyponatremia is known to commonly occur in certain infections, its association with melioidosis has not been studied previously. We studied incidence and impact of hyponatremia on clinical outcomes in melioidosis. Methods: This was a retrospective analysis of a single-center hospital registry of culture-positive patients with melioidosis hospitalized during a 10-year period (January 01, 2010, through January 31, 2021). Hyponatremia was defined as serum sodium of <135 mmol/L, and severe hyponatremia as serum sodium <120 mmol/L. The association of hyponatremia with in-hospital mortality, need for intensive care unit (ICU) stay and mechanical ventilation was studied. Results: Of 201 patients with melioidosis, 169 (84.1%) had hyponatremia, with severe hyponatremia in 35 (17.4%) patients. Older age (adjusted odds ratios [OR] 1.03, 95% confidence intervals [CI]: 1.00-1.06; P = 0.049) and acute kidney injury (AKI) (adjusted OR 3.30, 95% CI: 1.19-9.19; P = 0.02) were independently associated with hyponatremia. Twenty-two patients had been evaluated for cause of hyponatremia and of these, 11 (50%) had syndrome of inappropriate antidiuresis. Severe hyponatremia was associated with in-hospital mortality (adjusted OR 3.75, 95% CI: 1.37-10.27; P = 0.01), need for ICU stay (adjusted OR 7.04, 95% CI: 2.88-17.19; P < 0.001) and mechanical ventilation (adjusted OR 3.99, 95% CI: 1.54-10.32; P = 0.004). Conclusion: Hyponatremia occurs in 84.1% of hospitalized patients with melioidosis. Older age and AKI are associated with a higher incidence of hyponatremia. The presence of severe hyponatremia is an independent predictor of in-hospital mortality, need for mechanical ventilation and ICU stay.

Diabetic Retinopathy Is a Predictor of Progression of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis.

Methods: A systematic search was conducted on PubMed, Embase, and the Google scholar for eligible studies through September 2021. The quality of selected articles was assessed using JBI checklist. Higgins and Thompson's I 2 statistic was used to see the degree of heterogeneity. Based on degree of heterogeneity, fixed or random effects model was used to estimate pooled effect using inverse variance method. Results were expressed as hazard ratios and odds ratios with 95% CIs. Results: After scrutinizing 18017 articles, data from ten relevant studies (seven prospective and three retrospective) was extracted. DR was significantly associated with DKD progression with a pooled HR of 2.42 (95% CI: 1.70-3.45) and a pooled OR of 2.62 (95% CI: 1.76-3.89). There was also a significant association between the severity of DR and risk of progression of DKD with a pooled OR of 2.13 (95% CI: 1.82-2.50) for nonproliferative DR and 2.56 (95% CI: 2.93-.33) for proliferative DR. Conclusion: Our study suggests that presence of DR is a strong predictor of risk of kidney disease progression in DKD patients. Furthermore, the risk of DKD progression increases with DR severity. Screening for retinal vascular changes could potentially help in prognostication and risk-stratification of patients with DKD.

Measurement of Blood Pressure in Chronic Kidney Disease: Time to Change Our Clinical Practice - A Comprehensive Review.

Chronic kidney disease (CKD) is extremely common all over the world and is strongly linked to cardiovascular disease (CVD). The great majority of CKD patients have hypertension, which raises the risk of cardiovascular disease (CVD), end-stage kidney disease, and mortality. Controlling hypertension in patients with CKD is critical in our clinical practice since it slows the course of the disease and lowers the risk of CVD. As a result, accurate blood pressure (BP) monitoring is crucial for CKD diagnosis and therapy. Three important guidelines on BP thresholds and targets for antihypertensive medication therapy have been published in the recent decade emphasizing the way we measure BP. For both office BP and out-of-office BP measuring techniques, their clinical importance in the management of hypertension has been well defined. Although BP measurement is widely disseminated and routinely performed in most clinical settings, it remains unstandardized, and practitioners frequently fail to follow the basic recommendations to avoid measurement errors. This may lead to misdiagnosis and wrong management of hypertension, especially in CKD patients. Here, we review presently available all BP measuring techniques and their use in clinical practice and the recommendations from various guidelines and research gaps emphasizing CKD patients.

Outcomes and predictors of failure of arteriovenous fistulae for hemodialysis.

PURPOSE: Arteriovenous fistula(AVF) is preferred vascular access for hemodialysis but has primary failure in 20-60%. Studying predictors of AVF failure would help plan appropriate management.We studied AVF outcomes, clinical and vascular factors predicting their failure in patients requiring hemodialysis. METHODS: Retrospective study of patients with AVF creation from January 2017 to December 2018. Outcomes studied were immediate (< 72 h), primary (3 months) AVF failure, six-month/one-year patency, analyzed for predictive clinical, vascular factors as assessed using Pre-operative Doppler Ultrasound(DUS). RESULTS: Of 530 AVFs in 460 patients, DUS was done in 426/530 (80.4%), 349/460 (75.8%) were males, mean age was 53.10 ± 14.54 (18-91), 215/460(46.7%) had Diabetes mellitus(DM), 423/460(92%) hypertension. AVFs were radiocephalic in 79/530 (14.9%), brachiocephalic 418/530 (78.9%), brachiobasilic 33/530 (6.2%). AVF Immediate/Primary failure was seen in 64/530 (12.1%), 90/352 (25.6%); Patency at six months/one year in 253/352(71.8%),191/305 (62.6%), respectively. Older age had less immediate failures (AOR 0.97, CI 0.95-0.99, p 0.03). Feeding arterial diameter predicted immediate and primary failure on univariate analysis [OR 0.64 (95% CI 0.49-0.83), 0.62 (95% CI 0.47-0.89), respectively], but not multivariate. Artery diameter of > 4.0 mm had less failures [immediate (p 0.01), primary (p 0.02)], < 2.0 mm had specificity 95.9% and 95.4% for immediate, primary failure respectively. CONCLUSION: AVF failure is 12.1%, immediately; 25.6% three months after construction, Patency at 6 months is 71.8%, one year 62.6%. Immediate failures decrease with age. Artery diameters > 4.0 mm had less, < 2.0 mm had more failures.

Decision-making around Commencing Dialysis.

The decision regarding dialysis initiation is complex. Awareness that renal replacement therapy should not be regarded as default therapy for every patient with advanced renal failure is necessary. Decision to initiate dialysis and modality should be individualized in a shared decision-making process involving the treating nephrologist and the patient. Patients should receive predialysis education early in the course of chronic kidney disease so as to help prepare them well in advance for this eventuality. Withholding dialysis may be a reasonable option in a certain subset of patients, especially elderly patient with multiple co-morbid illnesses. Comprehensive conservation care should be offered in all patients where the decision to not dialyze is taken.

Sodium-glucose cotransporter-2 inhibitors and non-steroidal mineralocorticoid receptor antagonists: Ushering in a new era of nephroprotection beyond renin-angiotensin system blockade.

The therapeutic options for preventing or slowing the progression of chronic kidney disease (CKD) have been thus far limited. While angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are, without a doubt, safe and effective drugs, a significant proportion of patients with CKD still progress to end-stage kidney disease. After decades of negative trials, nephrologists have finally found cause for optimism with the introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and non-steroidal mineralocorticoid receptor antagonists (MRAs). Recent trials such as EMPA-REG OUTCOME and CREDENCE have provided evidence of the renal benefits of SGLT2 inhibitors, which have now found widespread acceptance as first-line agents for diabetic CKD, in addition to ACEi/ARBs. Considering results from the DAPA-CKD study, it is expected that their use will soon be expanded to other causes of albuminuric CKD as well, although confirmation from further trials, such as the EMPA-KIDNEY study is awaited. Likewise, although the role of mineralocorticoid receptor overactivation in CKD progression has been known for decades, it is only now with the FIDELIO-DKD study that we have evidence of benefits of MRAs on hard renal endpoints, specifically in patients with diabetic CKD. While further research is ongoing, given the evidence of synergism between the three drug classes, it is foreseeable that a combination of two or more of these drugs may soon become the standard of care for CKD, regardless of underlying aetiology. This review describes pathophysiologic mechanisms, current evidence and future perspectives on the use of SGLT2 inhibitors and novel MRAs in CKD.

Acute Kidney Injury and Progressive Diabetic Kidney Disease: An Epidemiological Perspective.

PURPOSE: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD. PATIENTS AND METHODS: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 - August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes. RESULTS: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (±4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018-1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m2/year (IQR-5.58-13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06-11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p<0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR. CONCLUSION: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.

Acute kidney injury and its outcomes in melioidosis.

BACKGROUND: Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. AIM: This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis. METHODS: A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI. RESULTS: Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140-29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67-21.22, P < 0.001) and shock (OR 3.75; CI 1.63-8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66-68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15-21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9-13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92-24, P = 0.002) and stage 3 (OR 17.8, CI 5.05-62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%). CONCLUSIONS: AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors.