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.

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.

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.

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.

Predictive Value of Camera-based Donor Glomerular Filtration Rate Estimation on the Immediate Renal Allograft Outcome Following Live-related Renal Transplant: A Single-center Retrospective Study.

Purpose of the Study: The purpose of this study was to assess the association of measured glomerular filtration rate (mGFR) using camera-based method with early transplant outcomes. Methodology: Diethylenetriamine pentaacetate renograms of all voluntary kidney donors between January 2016 and December 2022 at Kasturba Hospital, Manipal, India, were retrieved for the study. Recipients' posttransplant biochemical parameters were collected and compared against donors with scaled mGFR >80 ml/min/1.73 m2 (Group 1) and with mGFR between 60 and 80 ml/min/1.73 m2 (Group 2). Donor-recipient pair age, anthropometric parameters, and their differences were also assessed against the immediate transplant outcome. Posttransplant immediate graft function was assessed by posttransplant nadir serum creatinine, day to achieve nadir serum creatinine, the incidence of slow graft or delayed graft function, and serum creatinine at 1-month posttransplantation. Recipients with serum creatinine of >2.5 mg/dl on posttransplant day 7 were taken as slow graft function. Results: A total of 161 donor-recipient pairs were analyzed in the study. In recipients who showed persistently high serum creatinine posttransplant, older donor age(p < 0.001), higher difference in body mass index among the donor-recipient pair (p= 0.03), and mGFR <80ml/min (p < 0.001) were significantly associated. Slow graft function was significantly more in Group II recipients, with donors having mGFR <80ml/min as compared to Group I with mGFR >80 ml/min (37.3% vs. 10.6%) (P < 0.001). Conclusions: Camera-based mGFR using Gates' formula is a reliable tool to predict inferior graft outcomes in the immediate posttransplant period. Kidneys from donors with mGFR of 60-80 mL/min/1.73 m2 are likely to experience slow graft function in the immediate posttransplant period.

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.

Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Rare Tumour.

Subcutaneous Panniculitis like T cell Lymphoma (SPTCL) is an uncommon variant and poorly differentiated type of cutaneous T cell lymphoma. Here we describe the case of a 19-year-old female who presented with swelling of left half of the face with no regional lymphadenopathy and hepatosplenomegaly which was initially misdiagnosed as a benign cutaneous condition by various practitioners. Histopathological examination revealed diffuse infiltration of subcutaneous plane by small to medium sized atypical lymphocytes. Immunohistochemistry showed CD3, CD8 and ßF-1 positivity; CD20, CD56, Epstein Barr Virus (EBV) and TCR-δ negativity. Clinical profile, histopathology and immunohistochemical analysis yielded a diagnosis of SPTCL. Thus cases with atypical and nonresolving dermatological lesions should raise a suspicion of SPTCL as diagnosis against other benign conditions.