Kidney transplantation in patients on anti-tubercular therapy: A single centre observational study.

BACKGROUND: Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT). METHODS: This was a retrospective single-center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT. RESULTS: Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosed by ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post-transplantation fluoroquinolone-based non-rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post-transplantation was 71.9, 64.7, and 67 mL/min/1.73m2, respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%. CONCLUSION: Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase of ATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB.

An Intriguing Case of Amyloidosis Leading to PAGE Kidney in a Post Renal Transplant Recipient: A Case Report.

Amyloidosis is an infiltrative disease where amyloid fibrils get deposited in the organs like kidney, liver and spleen. Amyloid deposition in the kidneys classically meant deposition in the glomeruli and mesangium until 2008 when interstitial amyloid deposits were isolated and named as` Leukocyte cell-derived chemotaxin 2-associated amyloidosis. It is a progressive disease which clinically manifests as slowly progressive renal dysfunction and/or proteinuria. Our case 34 year old renal transplant recipient underwent graft biopsy post transplantation which revealed interstitial LECT-2 amyloid deposits. Unfortunately, he developed page kidney post biopsy which was managed conservatively with percutaneous drainage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01072-6.

Photocatalytic Hydrogen Evolution by a De Novo Designed Metalloprotein that Undergoes Ni-Mediated Oligomerization Shift.

De novo metalloprotein design involves the construction of proteins guided by specific repeat patterns of polar and apolar residues, which, upon self-assembly, provide a suitable environment to bind metals and produce artificial metalloenzymes. While a wide range of functionalities have been realized in de novo designed metalloproteins, the functional repertoire of such constructs towards alternative energy-relevant catalysis is currently limited. Here we show the application of de novo approach to design a functional H2 evolving protein. The design involved the assembly of an amphiphilic peptide featuring cysteines at tandem a/d sites of each helix. Intriguingly, upon NiII addition, the oligomers shift from a major trimeric assembly to a mix of dimers and trimers. The metalloprotein produced H2 photocatalytically with a bell-shape pH dependence, having a maximum activity at pH 5.5. Transient absorption spectroscopy is used to determine the timescales of electron transfer as a function of pH. Selective outer sphere mutations are made to probe how the local environment tunes activity. A preferential enhancement of activity is observed via steric modulation above the NiII site, towards the N-termini, compared to below the NiII site towards the C-termini.

Rational Design of a Cu Chelator That Mitigates Cu-Induced ROS Production by Amyloid Beta.

Alzheimer's disease severely perturbs transition metal homeostasis in the brain leading to the accumulation of excess metals in extracellular and intraneuronal locations. The amyloid beta protein binds these transition metals, ultimately causing severe oxidative stress in the brain. Metal chelation therapy is an approach to sequester metals from amyloid beta and relieve the oxidative stress. Here we have designed a mixed N/O donor Cu chelator inspired by the proposed ligand set of Cu in amyloid beta. We demonstrate that the chelator effectively removes Cu from amyloid beta and suppresses reactive oxygen species (ROS) production by redox silencing and radical scavenging both in vitro and in cellulo. The impact of ROS on the extent of oxidation of the different aggregated forms of the peptide is studied by mass spectrometry, which, along with other ROS assays, shows that the oligomers are pro-oxidants in nature. The aliphatic Leu34, which was previously unobserved, has been identified as a new oxidation site.

Racemose neurocysticercosis simulating tuberculous meningitis.

We report a patient with racemose neurocysticercosis, highlighting the diagnostic and management issues. A 37-year-old male had headaches, fever, and seizures for 8 months. He had a positive tuberculin test, cerebrospinal fluid pleocytosis, and hydrocephalus and exudates on MRI. His symptoms rapidly resolved following antitubercular and prednisolone treatment. After 2 months, he was readmitted with headache and vomiting, and his brain MRI revealed communicating hydrocephalus with a cyst in the lateral ventricle and subarachnoid space, which was confirmed as neurocysticercosis on the third ventriculostomy. The patient was managed with dexamethasone and a ventriculoperitoneal shunt. This case highlights that meningitis symptoms, CSF pleocytosis, and positive tuberculin tests may not always suggest tubercular etiology.

Clinical profile and outcomes of COVID-19 patients with acute kidney injury: a tertiary centre experience from South India.

AIM: The rates of development of acute kidney injury (AKI) in COVID-19 have been variably reported from across the world. Prevalence and outcomes of AKI in hospitalised COVID-19 patients in India has not been studied well. METHODS: This was a retrospective observational study amongst adult hospitalised COVID-19 patients admitted at a tertiary care centre between May 1 and October 31, 2020. We estimated the prevalence of AKI and outcomes including mortality and acute kidney disease (AKD) at the time of discharge. Regression analysis was done to study the factors associated with mortality and AKD. RESULTS: Out of 2650 hospitalised patients with COVID-19, 190 (7.2%) patients developed AKI. Mean age of patients with AKI was 62.6 years, 81.6% were male. Comorbidities included diabetes mellitus in 72.1%, hypertension in 66.8%, heart disease in 30% and chronic kidney disease (CKD) in 22.6%. Most patients had stage 1 AKI (71.1%). Overall mortality in patients with AKI was 22.1%, 75% in those requiring dialysis and 74.5% in those requiring ICU. Amongst survivors without pre-existing CKD, 40.9% patients had acute kidney disease at the time of discharge. Higher age, stage 3 AKI and need for mechanical ventilation were associated with higher mortality. On multivariable regression, factors associated with AKD at discharge included pre-existing heart disease and severe albuminuria during hospitalisation. CONCLUSION: In our study population, we found a low prevalence of AKI. Mortality was high in AKI patients requiring ICU care and dialysis. Amongst survivors, a significant percentage had AKD at the time of discharge.

The prevalence and clinical characteristics of anti-HMGCR (anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) antibodies in idiopathic inflammatory myopathy: an analysis from the MyoCite registry.

This study aimed to determine the prevalence and clinical characteristics of anti-HMGCR antibodies in idiopathic inflammatory myositis (IIM) at a tertiary care centre in northern India. Data (adult and children) were retrieved from the MyoCite dataset, identifying patients with polymyositis, dermatomyositis, and antibody-negative IIM whilst fulfilling the ACR/EULAR criteria. SLE, sarcoidosis, and systemic sclerosis were included for comparison as disease controls. The baseline clinical profile, laboratory tests, and muscle biopsies were retrieved and analysed. Descriptive statistics and non-parametric statistics were used for comparison. Among 128 IIM (112 adults, 16 children, M:F 1:2.8) of age 37 (24-47) years and 6 (3-17) months disease duration, 4 (3.6%) young adults tested positive for anti-HMGCR antibodies. All children and disease control tested negative for the antibody. Anti-HMGCR + IIM exhibited higher muscle enzymes [AST (367 vs 104 IU/L, p = 0.045), ALT (502 vs 78 IU/L, p = 0.004), and CPK (12,242 vs 699 IU/L, p = 0.001] except lactate dehydrogenase with less frequent systemic features such as fatigue than antibody-negative IIM. One young girl presented with a Limb-girdle muscular dystrophy (LGMD) with chronic pattern. None of the patients exhibited rashes, statin exposure, or cancer, though one had anti-Ro52 and mild disease. Our observations depict a younger population while affirming previous literature, including NM-like presentation, and chronic LGMD-like pattern of weakness in one case. Although a small number of children were included, ours is one of the few paediatric studies that evaluated HMGCR antibodies thus far. Further investigations in a larger Indian cohort are warranted to substantiate our findings.

Biosynthetic Approaches towards the Design of Artificial Hydrogen-Evolution Catalysts.

Hydrogen is a clean and sustainable form of fuel that can minimize our heavy dependence on fossil fuels as the primary energy source. The need of finding greener ways to generate H2 gas has ignited interest in the research community to synthesize catalysts that can produce H2 by the reduction of H+ . The natural H2 producing enzymes hydrogenases have served as an inspiration to produce catalytic metal centers akin to these native enzymes. In this article we describe recent advances in the design of a unique class of artificial hydrogen evolving catalysts that combine the features of the active site metal(s) surrounded by a polypeptide component. The examples of these biosynthetic catalysts discussed here include i) assemblies of synthetic cofactors with native proteins; ii) peptide-appended synthetic complexes; iii) substitution of native cofactors with non-native cofactors; iv) metal substitution from rubredoxin; and v) a reengineered Cu storage protein into a Ni binding protein. Aspects of key design considerations in the construction of these artificial biocatalysts and insights gained into their chemical reactivity are discussed.

Intrinsically fluorescent gold nanoclusters stabilized within a copper storage protein that follow the Irving-Williams trend in metal ion sensing.

Creating new environmentally friendly and non-toxic biomaterials with novel properties is required for numerous applications in healthcare and sensing. Protein bound gold nanoclusters constitute one such class of materials that offer promise in fluorescence imaging and sensing applications. However, unlike alkane thiol-protected gold nanoclusters, the number of protein-templated gold nanoclusters with such properties is limited and there is a need to expand the repertoire of such attractive hybrid quantum clusters. Herein, we report the synthesis, characterization, and applications of new fluorescent gold nanoclusters with tunable emission properties including blue, orange, and red, within a four-helix bundle copper storage protein (Csp1). The template protein consists of 13 cysteines along the length of the helix, which are suitable ligands to template Au and stabilize the resulting 14-19 atom clusters within the protein. The resulting clusters were extensively characterized by employing spectroscopic, microscopic and other analytical methods. The optical emission, relative quantum yields, and the excited state lifetime of the clusters are shown to depend on synthetic conditions. The clusters were found to be sensitive to the ppm level of transition metal ions with the quenching capabilities following the Irving-Williams series of metals (Co2+ < Ni2+ < Cu2+), which is rationalized based on the relative affinities of transition metals for a given set of ligands. The clusters were also found to be stable across the pH range 4-8.5 which, along with tunable emission properties paves the path for live bio-imaging and bio-sensing applications under physiological conditions.

A Unified View of Assessing the Pro-oxidant versus Antioxidant Nature of Amyloid Beta Conformers.

Transition-metal-catalyzed oxidative stress is a widespread concern in the pathogenesis of Alzheimer's disease. However, the exact role of amyloid beta oligomers towards oxidative stress is widely debated. Assessing the oxidative nature of the oligomers in vitro is complicated by the different experimental conditions under which they are prepared. We have investigated Cu2+ -catalyzed reactive oxygen species (ROS) generation by using oligomers prepared in phosphate-buffered saline (AßO-PBS ) and in cell culture medium (AßO-CCM ), and compared their activities with respect to the monomers and fibrils prepared at neutral and acidic pH. Although both are deca- to dodecamers, the AßO-PBS oligomers have a spherical morphology and are smaller than the AßO-CCM . The AßO-PBS behaved as pro-oxidants; in contrast, AßO-CCM quench OH. generation attributed to CCM itself. Although the pro-oxidant oligomers showed oxidation, they also partially protect themselves from radical damage and maintain their overall spherical arrangement. The monomers and fibrils manifested antioxidant properties: radical scavenging as opposed to redox silencing. A dual role of Aß species depending on the stage of the disease is proposed. In the earlier stages, the monomers can act as antioxidants, whereas at the later stages, the oligomers take on a pro-oxidant role. Kaempferol, a natural flavonoid, bound Cu2+ in 2:1 ratio and abolished ROS production in all Aß species. It also distinctly modified the folding landscape of Aß species into new or altered morphologies.

Tuberculosis in kidney transplant candidates and recipients.

Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

An Abysmal Quadrad: A Rare Case of Ankylosing Spondylitis, Ulcerative Colitis, and Takayasu Aortoarteritis Complicated by Secondary Renal Amyloidosis.

Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis that typically manifests in young males and may present with extra-articular manifestations. Takayasu aortoarteritis (TA) is a large vessel vasculitis that predominantly affects young and middle-aged females. Despite the limited number of studies examining the potential association between these two diseases, we report a unique case of an individual with ankylosing spondylitis and ulcerative colitis who subsequently developed Takayasu aortoarteritis. This progression ultimately led to the development of secondary renal amyloidosis, attributed to a combination of inflammatory pathologies.

Significance of histopathological features in the diagnosis of Budd-Chiari syndrome on liver biopsies.

Background: Budd-Chiari syndrome (BCS) requires a constellation of clinical, imaging, and histological findings for diagnosis. Liver biopsy serves as a tool for confirming the diagnosis, even though the histological characteristics are not pathognomonic. Aims: To determine which constellation of morphologic findings could aid in establishing a diagnosis of BCS in clinically suspected cases. Materials and Methods: A 5-year retrospective observational study was conducted. The clinical, laboratory, and histological findings of liver biopsies in patients with a clinical diagnosis of BCS were studied. Cases were segregated into two groups on the basis of the number of histological features present. A scoring system was then devised to assess the efficacy of the histological findings in diagnosing BCS. Statistical Analysis Used: The continuous variables were compared using the Mann-Whitney U-test, and categorical variables were compared using the Fisher-exact test. Results: The common histopathological findings were the presence of red blood cells in the space of disse (100%), peri-portal fibrosis (97.1%), sinusoidal dilation (97.1%), portal inflammation (67.6%), centrilobular necrosis (61.8%) and pericellular/sinusoidal fibrosis (61.8%). Comparison between the two groups showed that centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis were significant parameters. No correlation was found between the clinical and laboratory parameters and the two groups. Conclusions: The liver biopsy features in BCS are often nonspecific, and no single feature in isolation is characteristic. A constellation of features (centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis), when present together, indicate the possibility of BCS.

Unilateral Multicystic Dysplastic Kidney Management: A National Survey.

Risks of contralateral kidney abnormalities and chronic kidney disease necessitate follow-up for unilateral multicystic dysplastic kidneys (MCDK). A nationwide survey of senior UK pediatricians was conducted. Of the 60 responses obtained, 62% routinely perform a dimercaptosuccinic acid scan to confirm diagnosis. Eight percent routinely perform a cystogram to investigate contralateral vesicoureteric reflux. Sixty-two percent would routinely measure renal function (frequency ranging from once only to "every 2 years"). Twenty-five percent recalled MCDK nephrectomy being performed within the previous 5 years. Respondents voiced concerns that national guidance may result in an overcautious approach but could balance consensus and safe variation, and offer families choice and reassurance. The mean estimated cost of follow-up from birth to 18 years ranged from £258 to £3854. Results demonstrate significant variation in management, highlighting the need for a clear pathway to decrease unwanted variability and to ensure those at high risk of renal sequelae are recognized early, without undue investigatory burden.

Caught by Surprise - Microfilaria in Renal Biopsies.

Microfilarial parasites can obstruct the lymphatic tree giving rise to varying lymphatic and extra-lymphatic symptoms. Renal manifestations can range from asymptomatic proteinuria, chyluria, and nephrotic syndrome, to acute glomerulonephritis. The diagnosis of filariasis is usually made by the demonstration of the parasite in the peripheral blood smear, with or without eosinophilia. The renal involvement by this parasite has been sparsely reported in the literature. We hereby report five cases of filariasis detected on histopathological examination of renal biopsies, performed for other indications, along with a brief report of the additional histological findings. Three native and two graft biopsies were included. All our patients were male, with a mean age of 47 years (range 37 to 66 years). The serum creatinine ranged from 1.2 to 12.9 mg/dL. The mean 24-hour urinary protein was 3.6 gm/day. Peripheral blood eosinophilia was not recorded in any case, however, ESR was raised in all cases. Urine examination revealed varying proteinuria, with hematuria in two cases. Histological examination revealed microfilaria in all five biopsies, along with focal segmental glomerulosclerosis in two cases, combined cellular and humoral rejection, minimal change disease and acute tubular necrosis in one case each respectively. All patients were treated with diethylcarbamazine 6mg/kg/day or 12 days, in addition to the renal medications. Diagnosing the parasite is crucial as the patient is likely to benefit due to the timely treatment of the disease. Reporting this case series highlights an interesting finding in nephropathology.