Effect of chronic kidney disease on adverse drug reactions to anti-tubercular treatment: a retrospective cohort study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function. METHODOLOGY: This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio. RESULTS: Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p = 0.020]. CKD was an independent predictor for ADRs (OR -4.96, 95% CI: 2.79-8.82; p ≤ 0.0001). The matched cohort showed similar results. CONCLUSION: ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

Sonological predictors of complications of percutaneous renal biopsy-a prospective observational study.

Percutaneous renal biopsy, although essential for renal disease diagnosis, is associated with a number of post-biopsy complications ranging from gross haematuria to AV fistula to death. In this study, we carried out an active haematoma surveillance and attempted to correlate renal sonological parameters-kidney length, renal parenchymal changes, renal cortical and parenchymal thickness for their potential use in prediction of post-renal biopsy complications. METHODS: This was a prospective study done from April 2022 to April 2023 on all adult patients undergoing native or transplant kidney biopsy. Baseline clinical, laboratory and renal sonological parameters were noted prior to biopsy. USG-guided renal biopsy was done and any haematoma at 0 h, 12 h and 24 h post-biopsy noted. Biopsy complications including need for any interventions were noted. RESULTS: Out of the 240 patients enrolled in the study, 58.3% experienced post-biopsy complications. Among these, 5% of patients encountered major complications, with 3.33% necessitating medical intervention following renal biopsy procedures. A high percentage, 98.89%, exhibited hematoma formation within 12 h post-biopsy. Furthermore, our analysis revealed that a hematoma size exceeding 1.2 cm at the 12-h mark exhibited a sensitivity of 100% and specificity of 71% in predicting the need for blood transfusion. Renal parenchymal changes were the most reliable sonological parameters for predicting post-biopsy complication on multivariate analysis. CONCLUSION: The incidence of major complications requiring interventions following renal biopsy is notably low. Our study highlights the significance of renal sonological characteristics, including parenchymal thickness, cortical thickness and parenchymal changes, in predicting these complications. Furthermore, we emphasize the utility of hematoma surveillance immediately post-biopsy and at the 12 h, as a valuable tool for predicting the necessity of post-biopsy interventions. This approach can aid in efficiently triaging patients and determining the need for further observation post-renal biopsy.

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.

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.

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.

Effect of Febuxostat versus Allopurinol on the Glomerular Filtration Rate and Hyperuricemia in Patients with Chronic Kidney Disease.

Hyperuricemia is a risk factor for the progression of chronic kidney disease (CKD). We compared febuxostat versus allopurinol in the progression of CKD and hyperuricemia in 101 patients with Stage 3-4 CKD treated with febuxostat or allopurinol for at least 6 months for hyperuricemia (>7 mg/dL) between January 2012 and December 2016. Baseline characteristics, serum uric acid (SUA), serum creatinine, and estimated glomerular filtration rate (eGFR) at entry and 6 months were compared. The primary outcome was the decline in eGFR and the secondary outcomes were reductions in SUA and adverse events. Fifty-four were in the febuxostat group and 47 were in the allopurinol group. The baseline characteristics were comparable except for age. The mean dose of febuxostat and allopurinol was 43.70 ± 14.5 mg and 108.51 ± 40 mg, respectively. After 6 months, the median rate of decline in eGFR was 1.2 mL/min/1.73 m2 (IQR: 1.2, 5.5) in the febuxostat group and 3.1 mL/min/1.73 m2 (0.6, 6.2) in the allopurinol group, but this was not statistically significant (P = 0.136). The mean reduction in SUA was significantly better (P = 0.004) in the febuxostat group (3.9 ± 1.7 mg/dL) compared with the allopurinol group (2.1 ± 1.0 mg/dL). Both drugs had no serious adverse events. Febuxostat was better at reducing hyperuricemia than allopurinol, but there was no significant difference in the progression of CKD. Large randomized trials and long-term follow-up are necessary to see whether febuxostat has a favorable effect on the progression of CKD.

Frailty in end stage renal disease: Current perspectives / Fragilidad en la enfermedad renal en etapa terminal: perspectivas actuales

Frailty is common in end stage renal disease (ESRD) and is a marker of poor outcomes. Its prevalence increases as chronic kidney disease (CKD) progresses. There are different measurement tools available to assess frailty in ESRD. The pathogenesis of frailty in ESRD is multifactorial including uraemia and dialysis related factors. In this current review, we discuss the importance of frailty, its pathogenesis, screening methods, prognostic implications and management strategies in context of ESRD. (AU)

La fragilidad es común en la enfermedad renal en etapa terminal (ESRD) y es un marcador de malos resultados. Su la prevalencia aumenta a medida que avanza la enfermedad renal crónica (ERC). Hay diferentes herramientas de medición disponibles para evaluar la fragilidad en la ERT. La patogenia de la fragilidad en la ESRD es multifactorial que incluye uremia y factores relacionados con la diálisis. En esta revisión actual, discutimos la importancia de la fragilidad, su patogénesis, métodos de cribado, implicaciones pronósticas y estrategias de manejo en el contexto de la ESRD. (AU)

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.

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.

Frailty in end stage renal disease: Current perspectives.

Frailty is common in end stage renal disease (ESRD) and is a marker of poor outcomes. Its prevalence increases as chronic kidney disease (CKD) progresses. There are different measurement tools available to assess frailty in ESRD. The pathogenesis of frailty in ESRD is multifactorial including uraemia and dialysis related factors. In this current review, we discuss the importance of frailty, its pathogenesis, screening methods, prognostic implications and management strategies in context of ESRD.

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.

Hypertensive emergency and seizures during haemodialysis.

Intracranial abscesses are uncommon, serious and life-threatening infections. A brain abscess is caused by inflammation and collection of infected material, coming from local or remote infectious sources. Patients with chronic kidney disease on dialysis are prone to invasive bacterial infections like methicillin-resistant Staphylococcus aureus (MRSA) especially in the presence of central venous catheters or arteriovenous grafts. However, intracranial abscess formation due to MRSA is rare. Here, we present a case of MRSA brain abscess with an atypical clinical presentation in the absence of traditional risk factors.Intracranial abscesses are uncommon, serious, and life-threatening infections. A Brain abscess is caused by inflammation and collection of infected material, coming from local or remote infectious sources. Patients with chronic kidney disease on dialysis are prone to invasive bacterial infections like methicillin-resistant staphylococcus aureus (MRSA) especially in the presence of central venous catheters or arterio-venous grafts. However intracranial abscess formation due to MRSA is rare. Here we present a case of MRSA brain abscess with an atypical clinical presentation in the absence of traditional risk factors. A 46-year-old male with chronic kidney disease (CKD) secondary to chronic glomerulonephritis, on haemodialysis for 4 years through a left brachio-cephalic AVF developed an episode of generalised tonic-clonic seizures lasting 2 min during his scheduled dialysis session. He reported no complaints before entry to the dialysis. On clinical examination, he was drowsy with the absence of any focal motor deficits. His blood pressure was recorded to be 200/120 mm Hg. He was managed in the intensive care unit with mechanical ventilation, intravenous nitroglycerine for blood pressure control, levetiracetam for seizures and empirical vancomycin. Radiological evaluation showed a brain abscess in the midline involving bosth basi-frontal lobes. After medical optimization, the abscess was drained surgically, and the pus cultured. As culture grew Methicillin Resistant Staphylococcus aureus, he was treated with intravenous vancomycin for 6 weeks. On follow up, the abscess had resolved and the patient recovered without any neurological deficits.

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.

Comprehensive Conservative Care in End-Stage Kidney Disease.

In patients with end-stage kidney disease (ESKD), when there maybe situations where dialysis does not offer benefits in terms of survival or health-related quality of life, dialysis should not be viewed as the default therapy. Such patients can be offered comprehensive conservative care as an alternative to dialysis. Conservative (nondialytic) management of ESKD includes careful attention to fluid balance, treatment of anemia, correction of acidosis and hyperkalemia, blood pressure, and calcium/phosphorus metabolism management and dietary modification. Individualized symptom management and supportive care are crucial to maximize the quality of life. We propose that model of comprehensive conservative care in ESKD should manage both diseases as well as provide supportive care. Facilitating implementation of comprehensive conservative care requires coordination between nephrology and palliative care at patient, professional, administrative, and social levels to maximize benefit with the motto to improve the overall quality of life.