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Opportunistic infections or pathogens that reactivate from latent infection in the renal transplant recipients often arise during the peak immunosuppression period and infections such as Pneumocystis jirovecii may arise in the late period of posttransplant. In developing countries, tuberculosis (TB) is a major concern among transplant patients. Here, we present a case of 42-year-old male who presented after 10 years of renal transplant with a history of fever. On evaluation, he was diagnosed to have concomitant multiple infections like disseminated TB, Cryptococcal meningitis, Cytomegalovirus viremia, and Pneumocystis infection. He was treated with appropriate antibiotics, antifungal, and antiviral with close monitoring of drug-related side effects and graft function. Detailed evaluation and to look for concomitant infections is required for transplant patients who had no response to one particular group of drugs after initial diagnosis. He had stable graft function and developed drug-related side effects which required dose reduction intermittently. This case taught us how to manage four major infections with balancing immunosuppression, antibiotics, and graft function that we see in day-to-day practice of transplant clinics.

Introduction: The aim of the study was to study the clinical profile and outcomes of nocardiosis in renal allograft recipients. Methods: This was a retrospective study of clinical outcomes in consecutive renal allograft recipients with Nocardia infection over a 22-year period (2000–2022) from a tertiary care center in Southern India. The clinical data were obtained from electronic medical records and patient files. Results: A total of 1970 patients underwent renal transplantation at Christian Medical College, Vellore, India, between January 1, 2000, and December 31, 2022. During this period, 26 patients were diagnosed to have Nocardia infection. Half (50%) of the patients had fever and cough as their initial presentation, 7 (26.9%) patients presented with cutaneous abscesses, 2 (7.6%) patients were incidentally detected to have lung nodules during routine follow-up, 2 (7.6%) patients presented with headache accompanied by fever, and 3.8% had graft abscess. The diagnosis was made by isolating the organism in culture from one or more of the following samples: sputum, blood, pus, or lung biopsy (either computed tomography [CT]-guided or bronchoscopic aspirate culture). Eight patients required bronchoscopy and two patients required CT-guided biopsy for obtaining samples for diagnosis. All patients were similarly managed initially with a reduction of immunosuppression and appropriate antibiotics as per culture sensitivity. All 26 patients responded to induction treatment with meropenem (or imipenem) and trimethoprim–sulfamethoxazole (co-trimoxazole) followed by maintenance treatment with co-trimoxazole. Five (19.2%) out of 26 patients received Minocycline in induction and maintenance treatment regimens as in four patients isolates were resistant and one patient had allergic reaction to Cotrimoxazole. All patients had stable graft function. Two patients succumbed after 2 months of diagnosis with Gram-negative sepsis. Conclusions: At present, there exists no single serological test to diagnose Nocardia infection in patients. Multiple initially obtained cultures may be negative because of the slow growth of the organism and variable colony morphology. Hence, infected specimens should be obtained by aggressive approaches if the index of suspicion is high. Procedures such as bronchoscopic lavage and aspiration of abscess are invaluable toward making a diagnosis. In our study, eight patients required invasive diagnostic procedures such as bronchoalveolar lavage and CT-guided lung biopsy since initial Gram stain and sputum culture were negative. In conclusion, it is crucial to maintain a high level of suspicion and conduct thorough investigations among post renal transplant recipients. This approach facilitates early diagnosis, prompt initiation of appropriate treatment which helps prevent the spread of disease.

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9–30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft “mesangiolysis” was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). “Associated extra-renal GvHD” occurred in 11/19 (57.9%) allogenic recipients. Patients with “associated extra-renal GvHD” had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without “associated extra-renal GvHD” after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

In this case report, we present a renal transplant recipient who developed an infection due to a plant pathogen – Pantoea agglomerans. This pathogen is a rare organism with no case reports in a renal transplant recipient from India so far. A 50-year-old renal transplant recipient presented with fever for 20 days associated with productive cough and upper back pain. She had received her graft kidney 8 months earlier in a deceased donor program in her local state. In the immediate postoperative period, she had one episode of a mixed rejection, which required a course of antithymocyte globulin and plasmapheresis. On examination, tenderness was noted in her upper back over the cervical and thoracic vertebrae. Her computed tomography scan showed a collection over the cervical vertebrae and consolidation in the lung. Blood culture grew P. agglomerans. P. agglomerans is a rare plant pathogen usually occurring after trauma involving organic debris being deposited within the body. Spontaneously occurring infection is seen only in special situations such as immunocompromised states, malignancy, or excessive antacid use. It has been known to cause lung infections, bone and joint infections, and fever with systemic signs. Spontaneously occurring infections like in this patient are very rare with a handful of case reports worldwide. In an immunocompromised host, a multitude of infections can occur. This case report highlights the importance of removing unnecessary medication from our transplant recipients and optimizing immunosuppression while pursuing the underlying microbiologic cause of infection aggressively.

Introduction: Glomerular Research And Clinical Experiments—IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgA nephropathy (IgAN) cohort with prespecified objectives, protocolized longitudinal follow-up, and extensive biosample collection. The baseline risk scores predicted high risk of kidney disease progression. Methods: A total of 195 of 201 patients (97%) completed 3-year follow-up in September 2020. All patients received optimized supportive care, and those at high risk of progression were offered systemic corticosteroids. Results: A total of 76 patients (76 of 193, 39.4%) had rapid progression in 3 years (≥5 ml/min per 1.73 m2 decline in estimated glomerular filtration rate [eGFR] per year). A total of 72 patients (72 of 195, 36.9%) experienced the composite outcome (CO), defined as ≥50% fall in eGFR, eGFR < 15 ml/min per 1.73 m2, commenced kidney replacement therapy or death, in 3 years. At each scheduled follow-up, achievement of proteinuria level < 1 g/d significantly delayed the time to the CO. The receiver operating characteristic curve of average annual decline in eGFR ≥ 5 ml/min per 1.73 m2 had 86% sensitivity and 89% specificity for CO in 3 years and had good discrimination from 1 year onwards (area under the curve 0.8, SE 0.04, 95% CI 0.7–0.9, P < 0.0001). The significant predictors of CO by Cox proportional-hazards model were as follows: baseline MEST-T2 score (hazard ratio [HR] 3.3, 95% CI 1.7–6.5, P < 0.001), along with 24-hour urine protein level ≥ 1 g/d (HR 2.1, 95% CI 1.1–3.9, P = 0.02), eGFR < 60 ml/min per 1.73 m2 (HR 2.9, 95% CI 1.1–7.6, P = 0.03), and rate of eGFR decline ≥ 5 ml/min per 1.73 m2/yr (HR 2.7, 95% CI 1.6–4.8, P < 0.001) all measured at 6 months. Mortality was 11 of 195 (5.6%). Conclusion: We identified longitudinal clinical variables measured at 6 months and ≥5 ml/min per 1.73 m2 annual fall in eGFR after kidney biopsy as important predictors for composite outcome in addition to baseline histology.

Dual anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) characterized by the presence of both anti-proteinase-3 (PR3-ANCA) and anti-myeloperoxidase (MPO-ANCA) antibodies is a rare clinical entity. Only few cases have been reported previously, most of which were associated with infections, drugs, autoimmune diseases and malignancies. Herein, we describe a young woman who presented with rapidly progressive glomerulonephritis with hypocomplementemia and markedly elevated anti-PR3 and anti-MPO titres. Meticulous work-up ruled out all possible secondary causes. Renal biopsy showed the presence of focal fibrocellular crescents with focal mesangial hypercellularity. Immunofluorescence and electron microscopy showed pauci-immune deposits. The patient was treated with an induction regimen comprising oral prednisolone and cyclophosphamide. She attained both clinical and serological remission at 3 months and is currently on an azathioprine-based maintenance regimen. We have extensively reviewed all previous cases of dual AAV and have formulated an approach to diagnose and treat this rare entity.

Background: The spectrum and outcomes of crescentic glomerulonephritis (Cr.GN) in South Asia is vastly different from that reported worldwide and there is a paucity of information. The aim of the study was to study the demography, clinical presentation, histology and predictors of longitudinal outcomes of Cr.GN in this population. Methods: An observational cohort study of renal biopsies was performed in the largest tertiary center in South India over a period of 10 years (January 2006 to December 2015) with ≥50% crescents on renal histology indicating Cr.GN. Results: A total of 8645 kidney biopsies were done; 200 (2.31%) were Cr.GN. Patients were categorized into three etiological groups: anti-glomerular basement membrane (type I), immune complex (type II), and pauci-immune (type III). Type II was the most common (96, 46.5%), followed by type III (73, 38%) and type I (31, 15.5%). Female preponderance was seen across all types. About half of all patients presented with recent onset hypertension. Type II had the highest median proteinuria (4.2 (2.1-6) g/day, p=0.06) and the median estimated glomerular filtration rate was lowest in type I (5 (4-8) ml/min/1.73m2, p

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI— Glomerular Research And Clinical Experiments- IgA Nephropathy in Indians—cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.

The editorial discusses novel pathophysiologic mechanisms and reno-protective pharmacotherapies in diabetic kidney disease (DKD). It highlights the importance of sodium glucose co-transporter-2 inhibitors (SGLT-2i) in managing DKD and the discovery of newer therapies targeting diverse pathophysiologic pathways. The research topic aims to understand complex mechanisms, identify therapeutic targets, and test agents in well-designed clinical trials. Various studies explore the role of different medications, such as semaglutide, Chinese herbal medicines, Huangkui capsule, and Ophiocordyceps sinensis, in treating DKD by addressing oxidative stress, inflammation, and other pathogenic pathways. [Extracted from the article]

Background: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD. Summary: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30–50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin. Key Messages: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding. [ABSTRACT FROM AUTHOR]