A Case of Erythropoietin (EPO)-Induced Pure Red Cell Aplasia and Its Treatment Efficacy With Desidustat.

Pure red cell aplasia (PRCA), a rare hematological disorder marked by severe anemia and reticulocytopenia, results from the near absence of developing erythroid precursors in the otherwise normal bone marrow. This case report focuses on a 48-year-old female with chronic kidney disease (CKD) who received erythropoietin injections for CKD-related secondary anemia. Despite an initial positive response, a sudden drop in hemoglobin levels prompted investigations, revealing endogenous erythropoietin (EPO)-induced PRCA due to anti-EPO antibodies. In response, desidustat, an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor, was successfully introduced as an alternative treatment. This led to a substantial and sustained improvement in hemoglobin levels, emphasizing the crucial role of swift diagnosis and intervention in EPO-induced PRCA cases. Administration method and storage conditions are noteworthy factors influencing recombinant human erythropoietin (rHuEPO) immunogenicity. The case underscores desidustat's emergence as a less immunogenic and effective alternative for anemia, marking a significant advancement, particularly in the context of this pioneering case in India showcasing its efficacy.

Renal Aspergillosis Complicating Renal Allograft Transplantation: A Case Report.

Renal aspergillosis is a rare yet potentially devastating complication following renal allograft transplantation. We present the case of a 45-year-old male with a history of crescentic IgA nephropathy who underwent renal allograft transplantation from his mother. Despite initial favorable progress, he developed post-transplant renal dysfunction attributed to active antibody-mediated rejection. Subsequently, he presented with signs of systemic infection and graft dysfunction, leading to the diagnosis of renal aspergillosis. Despite aggressive management, including antifungal therapy and cessation of immunosuppression, the patient progressed to renal graft cortical necrosis, necessitating nephrectomy. This case underscores the challenges in diagnosing and managing renal aspergillosis in transplant recipients and highlights the importance of early recognition and prompt intervention to improve outcomes in such cases.

Infection-Related Glomerulonephritis Due to Subacute Bacterial Endocarditis in the Aortic Valve: A Case Report.

Infection-related glomerulonephritis (IRGN) is a rare but severe complication of bacterial infections, including subacute bacterial endocarditis (SBE). We present a case of a 15-year-old male with bilateral lower limb swelling, facial puffiness, frothy urine, and dyspnea. Laboratory investigations revealed abnormal kidney function tests and imaging studies confirmed infective endocarditis. Blood cultures isolated Burkholderia cepacia and methicillin-resistant coagulase-negative Staphylococcus. Kidney biopsy confirmed immune complex-mediated glomerulonephritis. The patient received multidisciplinary care, including respiratory support, hemodialysis, antibiotics, and blood transfusion. This case highlights the importance of recognizing and promptly managing IRGN secondary to SBE to prevent irreversible renal damage and systemic complications.

Bacterial exopolysaccharide amendment improves the shelf life and functional efficacy of bioinoculant under salinity stress.

AIM: Bacterial exopolysaccharides (EPS) possess numerous properties beneficial for the growth of microbes and plants under hostile conditions. The study aimed to develop a bioformulation with bacterial EPS to enhance the bioinoculant's shelf life and functional efficacy under salinity stress. METHODS AND RESULTS: High EPS-producing and salt-tolerant bacterial strain (Bacillus haynessi SD2) exhibiting auxin-production, phosphate-solubilization, and biofilm-forming ability, was selected. EPS-based bioformulation of SD2 improved the growth of three legumes under salt stress, from which pigeonpea was selected for further experiments. SD2 improved the growth and lowered the accumulation of stress markers in plants under salt stress. Bioformulations with varying EPS concentrations (1% and 2%) were stored for 6 months at 4°C, 30°C, and 37°C to assess their shelf life and functional efficacy. The shelf life and efficacy of EPS-based bioformulation were sustained even after 6 months of storage at high temperature, enhancing pigeonpea growth under stress in both control and natural conditions. However, the efficacy of non EPS-based bioformulation declined following four months of storage. The bioformulation (with 1% EPS) modulated bacterial abundance in the plant's rhizosphere under stress conditions. CONCLUSION: The study brings forth a new strategy for developing next-generation bioformulations with higher shelf life and efficacy for salinity stress management in pigeonpea.

A Rare Case of Carpenter Syndrome and Its Unique Association With Chronic Kidney Disease.

Carpenter syndrome, characterized by RAB23 mutations, is a rare autosomal recessive disorder distinguished by unique features such as craniofacial anomalies, congenital heart disease, brachydactyly, and obesity. This syndrome's rarity, with an estimated prevalence of one in a million births, poses diagnostic challenges due to its diverse clinical spectrum. Notably, this case report highlights an unusual association of Carpenter syndrome with chronic kidney disease (CKD), underscoring the need for further exploration into the syndromic interplay and shared genetic pathways. The distinctive manifestation of CKD in the context of Carpenter syndrome adds a novel dimension, emphasizing the importance of timely diagnosis and comprehensive care. Further research is warranted to unravel the intricate genetic and molecular pathways underlying the syndrome's diverse manifestations, shedding light on potential shared mechanisms and paving the way for targeted interventions and enhanced patient care.

A Case of NELL-1-Positive Membranous Nephropathy With Acute Kidney Injury Due to Bilateral Renal Vein Thrombosis.

Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in non-diabetic adults. It can be primary, attributed to autoantibodies targeting podocyte antigens, or secondary to various disorders. Although rare, nerve epidermal growth factor-like 1 (NELL-1)-associated MN presents diagnostic and management challenges. Thrombotic complications such as renal vein thrombosis (RVT) are recognized but less reported, especially in NELL-1-positive MN. We report a 43-year-old male with NELL-1-positive MN complicated by acute kidney injury (AKI) due to bilateral RVT, treated successfully with thrombolysis. Histopathological analysis confirmed MN with specific immunohistochemical staining for NELL-1. Treatment included immunosuppressive therapy and tailored anticoagulation. This case emphasizes recognizing thrombotic complications in MN, particularly in NELL-1-positive cases. Further research is needed to explore serum anti-NELL-1 antibodies as biomarkers and optimal anticoagulation strategies in MN patients at risk of thrombotic events to improve outcomes and guide personalized management.

Identification and development of Tetra-ARMS PCR-based screening test for a genetic variant of OLA1 (Tyr254Cys) in the human failing heart.

Obg-like ATPase 1 (OLA1) protein has GTP and ATP hydrolyzing activities and is important for cellular growth and survival. The human OLA1 gene maps to chromosome 2 (locus 2q31.1), near Titin (TTN), which is associated with familial dilated cardiomyopathy (DCM). In this study, we found that expression of OLA1 was significantly downregulated in failing human heart tissue (HF) compared to non-failing hearts (NF). Using the Sanger sequencing method, we characterized the human OLA1 gene and screened for mutations in the OLA1 gene in patients with failing and non-failing hearts. Among failing and non-failing heart patients, we found 15 different mutations in the OLA1 gene, including two transversions, one substitution, one deletion, and eleven transitions. All mutations were intronic except for a non-synonymous 5144A>G, resulting in 254Tyr>Cys in exon 8 of the OLA1 gene. Furthermore, haplotype analysis of these mutations revealed that these single nucleotide polymorphisms (SNPs) are linked to each other, resulting in disease-specific haplotypes. Additionally, to screen the 254Tyr>Cys point mutation, we developed a cost-effective, rapid genetic screening PCR test that can differentiate between homozygous (AA and GG) and heterozygous (A/G) genotypes. Our results demonstrate that this PCR test can effectively screen for OLA1 mutation-associated cardiomyopathy in human patients using easily accessible cells or tissues, such as blood cells. These findings have important implications for the diagnosis and treatment of cardiomyopathy.

Bortezomib-Induced Superficial Vasculitis in a Kidney Transplant Recipient: A Rare Case.

Bortezomib is a frequently administered immunosuppressive agent in kidney transplantation. A 30-year-old male kidney transplant recipient developed an atypical reaction on the left hand in terms of spider-like extensions, indicating erythematous inflammation along the superficial veins after bortezomib intravenous administration. The inflammation spontaneously resolved after three weeks with a bortezomib dose reduction. Nephrologists must be familiar with the potential cutaneous bortezomib-induced adverse effects.

Dapagliflozin-Induced Erythrocytosis in Chronic Kidney Disease: A Rare Occurrence.

Erythrocytosis, a rare adverse effect associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), has been reported in diabetic patients, but its occurrence in those with chronic kidney disease (CKD) remains underrecognized. Here, we present two cases of dapagliflozin-related erythrocytosis in diabetic patients with CKD, highlighting the need for increased awareness among clinicians. Despite the established efficacy of SGLT2i in managing type 2 diabetes mellitus (T2DM) and its cardiovascular benefits, erythrocytosis poses a potential complication, necessitating thorough understanding and monitoring. While the precise mechanism of SGLT2i-induced erythrocytosis remains unclear, hypotheses include hemoconcentration and modulation of iron metabolism. Notably, our cases demonstrate a rapid onset of erythrocytosis, possibly exacerbated by CKD, emphasizing the importance of vigilant hemoglobin monitoring, especially in CKD patients on SGLT2i therapy. Timely discontinuation of dapagliflozin resulted in a significant reduction in hemoglobin levels, underscoring the critical role of early intervention in preventing erythrocytosis-related complications. This report advocates for routine hematological evaluation in CKD patients treated with SGLT2i to promptly detect and manage erythrocytosis, enhancing patient safety and improving clinical outcomes.

Nephrotic Syndrome Due to Sunitinib: A Rare Complication of Treatment of Renal Cell Carcinoma.

This case report details a 62-year-old male with a history of right renal cell carcinoma (RCC) who developed sunitinib-induced nephrotic syndrome during treatment. The patient had a complex medical history, including a right nephrectomy in 2009, brain metastasis excisions in 2011 and 2012, and prolonged sunitinib therapy. Hypothyroidism, hypertension, and various surgeries further complicated his clinical picture. In April 2022, the patient presented with bilateral pedal edema, acute kidney injury superimposed on chronic kidney disease, and proteinuria. Upon examination, the decision was made to discontinue sunitinib, leading to the resolution of nephrotic syndrome. Adjustments in thyroxine dosage were made, and pharmacological interventions were employed to manage proteinuria and renal dysfunction. A multidisciplinary approach involving oncologists, nephrologists, and endocrinologists was essential in achieving a favorable outcome. The case highlights the intricate balance required in managing patients undergoing targeted cancer therapies, emphasizing the importance of vigilant monitoring, prompt intervention, and a collaborative approach for optimal patient care.

A Rare Case of Autoimmune Disorder as a Trigger for Atypical Hemolytic Uremic Syndrome.

Autoimmune diseases may act as a trigger for atypical hemolytic uremic syndrome (aHUS). Triggers for aHUS may include autoimmune diseases, infections, metabolic conditions, pregnancy, and transplants. aHUS-mediated injury to various organs, especially kidneys, can be life-threatening. Here, we present the case of a young female who had perinuclear antineutrophil cytoplasmic antibody (p-ANCA)-associated vasculitis and was diagnosed with aHUS. We consider underlying autoimmune p-ANCA-associated vasculitis as a trigger for aHUS in this case.

Renal Functional Reserve in Acute Kidney Injury Patients Requiring Dialysis.

The incidence of acute kidney injury (AKI) has increased in the recent past. Patients with AKI have an increased risk of mortality. They are also at increased risk of developing chronic kidney disease (CKD). AKI can lead to irreversible loss of renal function despite complete clinical recovery. Currently, no tools are available to diagnose this subclinical loss of renal function. Renal functional reserve (RFR) can serve as an essential tool for analyzing this subclinical loss of renal function, and patients with loss of RFR post-AKI may be closely followed for the development of CKD. This prospective observational study, conducted at the Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), aimed to investigate RFR in 223 patients with AKI requiring dialysis. The study excluded patients with CKD and obstructive uropathy. Methods included RFR assessment three months post-AKI recovery, utilizing technetium-99m (Tc-99m) diethylenetriaminepentaacetic acid (DTPA) plasma clearance during amino acid infusion. Statistical analyses and logistic regression were applied, receiving ethical approval. Results revealed a high in-hospital mortality rate of 78.02%, associated with elevated Sequential Organ Failure Assessment (SOFA) scores. Among 24 patients with complete AKI recovery, the RFR at three months was 10.06% (interquartile range (IQR) 5.60-20.15), with the measured GFR significantly lower than the estimated glomerular filtration rate (GFR). The study concludes that AKI requiring dialysis is linked to high mortality and emphasizes the predictive value of SOFA scores. Additionally, RFR testing at three months post-recovery provides insights into potential long-term impacts on renal function. This study contributes valuable insights into the prognosis of AKI patients requiring dialysis. It underscores the need for further research on RFR as a diagnostic tool and the lasting consequences of AKI.

Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.

We assessed the mechanisms by which nonencapsulated heme, released in the plasma of mice after exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult male and female C57BL/6 mice to Cl2 (500 ppm for 30 min), returned them to room air, and injected them intramuscularly with either human hemopexin (hHPX; 5 µg/g BW in 50-µL saline) or vehicle at 1 h post-exposure. Upon return to room air, Cl2-exposed mice, injected with vehicle, developed respiratory acidosis, increased concentrations of plasma proteins in the alveolar space, lung mitochondrial DNA injury, increased levels of free plasma heme, and major alterations of their lung proteome. hHPX injection mice mitigated the onset and development of lung and mitochondrial injury and the increase of plasma heme, reversed the Cl2-induced changes in 83 of 237 proteins in the lung proteome at 24 h post-exposure, and improved survival at 15 days post-exposure. Systems biology analysis of the lung global proteomics data showed that hHPX reversed changes in a number of key pathways including elF2 signaling, verified by Western blotting measurements. Recombinant human hemopexin, generated in tobacco plants, injected at 1 h post-Cl2 exposure, was equally effective in reversing acute lung and mtDNA injury. The results of this study offer new insights as to the mechanisms by which exposure to Cl2 results in acute lung injury and the therapeutic effects of hemopexin.NEW & NOTEWORTHY Herein, we demonstrate that exposure of mice to chlorine gas causes significant changes in the lung proteome 24 h post-exposure. Systems biology analysis of the proteomic data is consistent with damage to mitochondria and activation of eIF2, the master regulator of transcription and protein translation. Post-exposure injection of hemopexin, which scavenges free heme, attenuated mtDNA injury, eIF2α phosphorylation, decreased lung injury, and increased survival.

A Rare Case of Atypical Anti-glomerular Basement Membrane Disease.

Anti-glomerular basement membrane (Anti-GBM) disease is a severe form of glomerulonephritis (GN) that predominantly impacts individuals aged 20 to 70. It arises from the presence of circulating antibodies that specifically target an antigen inherent to the basement membranes of glomerular and alveolar structures. A unique subset within this category is termed atypical anti-GBM disease. In this variant, a distinctive feature is the widespread linear staining of the glomerular basement membrane (GBM) by IgG observed through immunofluorescence microscopy, with the notable absence of anti-GBM antibodies in the patient's serum. Here, we present an unusual case involving a 65-year-old female patient who sought medical attention due to rapidly progressing renal failure. The initial management included six hemodialysis sessions. Following a kidney biopsy, the diagnosis revealed a sclerosed phase of diffuse crescentic glomerulonephritis, attributed to atypical anti-GBM disease. Given the presence of diffuse crescents on the kidney biopsy, the medical team opted for an aggressive treatment regimen, commencing with intravenous methylprednisolone, followed by oral cyclophosphamide and oral prednisolone. Plasmapheresis was also recommended as part of the treatment plan, although it did not materialize due to the family's reluctance. Despite exhaustive efforts, the renal failure exhibited no signs of improvement, leading to the patient's discharge with a plan for ongoing maintenance hemodialysis. It is crucial to emphasize the pivotal role of immunosuppressive medications in managing this condition, as they play a critical role in preventing antibody formation and subsequent hypersynthesis that can exacerbate the disease.

Young Male With End-Stage Renal Disease Due to Primary Hyperoxaluria Type 2: A Rare Presentation.

Primary hyperoxaluria type 2 (PH2) is a rare genetic disorder characterized by excessive oxalate production due to glyoxylate metabolism alterations. This case report presents a 26-year-old male with PH2 who experienced recurrent nephrolithiasis since childhood, leading to end-stage renal disease (ESRD). The patient's history prompted genetic testing, which revealed a heterozygous missense variant in the GRHPR gene, confirming PH2. Early genetic diagnosis is crucial for preventing ESRD and planning effective treatments. Patients with PH2 require intensive hemodialysis and may benefit from kidney transplantation. However, even after transplantation, ongoing preventive measures are essential due to the risk of hyperoxaluria-related graft damage. This case highlights the importance of early detection and genetic testing in managing PH2 to delay ESRD and improve patient outcomes.

Nephrotic Syndrome in a Retroviral Disease Due to AA Amyloidosis: A Rare Presentation.

Kidney disease poses a significant burden on individuals with HIV infection. In the pre-ART era, HIV-associated nephropathy (HIVAN) was the most common renal pathology identified in individuals with HIV. However, the widespread use of ART has led to changes in the spectrum of renal pathologies associated with HIV. HIV infection is an unclear cause of AA amyloidosis. Here, we report a rare case of an HIV-positive patient presenting with nephrotic syndrome which turned out to be AA amyloidosis on renal biopsy.

When Venom Meets the Heart: A Rare Case of Scorpion Sting-Induced Acute Myocardial Infarction.

Scorpion sting cases are everyday encounters in the Emergency Department (ED). However, scorpion sting-induced systemic manifestations are rarely seen. Signs and symptoms of envenomation involve the central nervous system, stimulation of the autonomic nervous system and rarely respiratory and heart failure leading to death. Cardiovascular manifestations are particularly prominent following stings by the Indian red scorpion. This case report is of an 18-year-old male patient who presented to ED with complaints of scorpion sting. Twelve lead electrocardiography (ECG) done was suggestive of acute inferior wall myocardial infarction with raised cardiac markers. He also had autonomic dysfunction in the form of hypertension, hypothermia and priapism. He was treated with an alpha-blocker, dual antiplatelets and analgesics. ECG changes reverted to normal the next day, and he was discharged. So, the anticipation of life-threatening complications of scorpion stings plays a vital role in the treatment and prognosis of patients presenting to ED.

Lupus Nephritis With Collapsing Glomerulopathy: A Rare Association.

Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Crescentic lupus nephritis rarely presents as rapidly progressive renal failure (RPRF) and needs prompt initiation of treatment. Collapsing glomerulopathy (CG) itself is associated with poor renal survival. Collapsing glomerulopathy's association with lupus nephritis is rarely reported in the literature. It may indicate a severe form of lupus podocytopathy.

Identification and development of Tetra-ARMS PCR-based screening test for a genetic variant of OLA1 (Tyr254Cys) in the human failing heart.

Obg-like ATPase 1 (OLA1) protein has GTP and ATP hydrolyzing activities and is important for cellular growth and survival. The human OLA1 gene maps on chromosome 2, at the locus 1q31, close to the Titin (TTN) gene, which is associated with familial dilated cardiomyopathy (DCM). In this study, we found that expression of OLA1 was significantly downregulated in human failing heart tissue (HF) as compared to in non-failing heart tissues (NF). Moreover, using the Sanger sequencing method, we characterized the human OLA1 gene and screened genetic mutations in patients with heart-failing and non-failing. Among failing and non-failing heart patients, we found a total of 15 mutations, including two transversions, one substitution, one indel, and eleven transition mutations in the OLA1 gene. All the mutations were intronic except for a non-synonymous mutation, 5144A>G, resulting in 254Tyr>Cys in exon 8 of the OLA1 gene. Furthermore, haplotype analysis of these mutations revealed that these single nucleotide polymorphisms (SNPs) are linked to each other, resulting in disease-specific haplotypes. Additionally, to screen for the 254Tyr>Cys point mutation, we developed a cost-effective, rapid genetic screening PCR test that can differentiate between homozygous (AA and GG) and heterozygous (A/G) genotypes. Our results show that this test can be used as a genetic screening tool for human cardiomyopathy. These findings have important implications for the diagnosis and treatment of cardiomyopathy.

Composition of fungal communities upon multiple passaging of rhizosphere microbiome for salinity stress mitigation in Vigna radiata.

The top-down approach of microbiome-mediated rhizosphere engineering has emerged as an eco-friendly approach for mitigating stress and enhancing crop productivity. It has been established to mitigate salinity stress in Vigna radiata using multi-passaging approach. During the process of acclimatization under increasing levels of salinity stress, the structure of rhizospheric microbial community undergoes dynamic changes, while facilitating stress mitigation in plants. In this study, using ITS-based amplicon sequencing, the dynamics of rhizosphere fungal community was unravelled over successive passages under salinity stress in V. radiata. Clear shifts were evident among the fungal community members under stress and non-stress conditions, upon application of acclimatized rhizosphere microbiome in V. radiata across successive passages. These shifts correlated with enhanced plant biometrics and reduced stress marker levels in plant. Significant changes in the fungal community structure were witnessed in the rhizosphere across specific passaging cycles under salinity stress, which possibly facilitated stress mitigation in V. radiata.