Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS.

INTRODUCTION: In the advanced stage of chronic kidney disease (CKD), electrolytes, fluids, and metabolic wastes including various uremic toxins, accumulate at high concentrations in the patients' blood. Hemodialysis (HD) is the conventional procedure used worldwide to remove metabolic wastes. The creatinine and urea levels have been routinely monitored to estimate kidney function and effectiveness of the HD process. This study, first from in Indian perspective, aimed at the identification and quantification of major uremic toxins in CKD patients on maintenance HD (PRE-HD), and compared with the healthy controls (HC) as well as after HD (POST-HD). OBJECTIVES: The study mainly focused on the identification of major uremic toxins in Indian perspective and the quantitative analysis of indoxyl sulfate and p-cresol sulfate (routinely targeted uremic toxins), and phenyl sulfate, catechol sulfate, and guaiacol sulfate (targeted for the first time), apart from creatinine and urea in PRE-HD, POST-HD, and HC groups. METHODS: Blood samples were collected from 90 HD patients (both PRE-HD and POST-HD), and 74 HCs. The plasma samples were subjected to direct ESI-HRMS and LC/HRMS for untargeted metabolomics and LC-MS/MS for quantitative analysis. RESULTS: Various known uremic toxins, and a few new and unknown peaks were detected in PRE-HD patients. The p-cresol sulfate and indoxyl sulfate were dominant in PRE-HD, the concentrations of phenyl sulfate, catechol sulfate, and guaiacol sulfate were about 50% of that of indoxyl sulfate. Statistical evaluation on the levels of targeted uremic toxins in PRE-HD, POST-HD, and HC groups showed a significant difference among the three groups. The dialytic clearance of indoxyl sulfate and p-cresol sulfate was found to be < 35%, while that of the other three sulfates was 50-58%. CONCLUSION: LC-MS/MS method was developed and validated to evaluate five major uremic toxins in CKD patients on HD. The levels of the targeted uremic toxins could be used to assess kidney function and the effectiveness of HD.

Evaluation of amino acids and other related metabolites levels in end-stage renal disease (ESRD) patients on hemodialysis by LC/MS/MS and GC/MS.

End-stage renal disease (ESRD) is a rapidly increasing health problem, and every year, about 2 million ESRD cases are reported worldwide. Hemodialysis (HD) is the vital renal reinstatement therapy for ESRD, and HD patterns play a crucial role in patients' health. Plasma metabolomics is the potential approach to understanding the HD process, effectiveness, and patterns. The lack of protein vitality is a primary problem for HD patients, and the quantities of amino acids intracellularly and in the blood are considered to be a symbolic index of protein metabolism and nutrition conditions. In the current study, LC/MS/MS and GC/MS methods were developed for 29 targeted plasma metabolites and validated as per ICH bioanalytical method validation M10 guidelines. The 29 metabolites included 20 proteinogenic amino acids and nine other related metabolites. The methods were employed to measure the absolute quantities (µM) of the targeted metabolites in HD patients (n=60) before and after dialysis (PRE-HD and POST-HD), and compared with the healthy control (HC) group (n=60). Phenylacetylglutamine was found to be higher in both PRE-HD (72.88±14.5 µM) and POST-HD (26.62±7.9 µM), when compared to HC (1.61±0.6 µM). On the other hand, glutamic acid was lower in PRE-HD (14.90±6.5 µM), and POST-HD (13.6±6.1 µM) than that of HC (245.4±37.8 µM). The dialytic loss was found to be 52-45% for arginine, lysine, and histidine, while it was 38-26% for glycine, cysteine, proline, alanine, threonine, glutamine, valine, and methionine. The dialytic loss was low (≤12%) for aspartic acid, glutamic acid, asparagine, leucine, tyrosine, tryptophan, and isoleucine. Graphical abstract adapted from mass spectrometry templates by Biorender.com retrieved from https://app.biorender.com/biorender-templates .

Bilateral upper limb digital gangrene in a patient on maintenance hemodialysis.

Upper limb gangrene is uncommon compared to lower limb gangrene. But digital gangrene is seen occasionally in patients on maintenance hemodialysis. Of the various causes described, atherosclerosis, diabetic vascular disease, following AV fistula surgery were few of the causes. Herein, we report a case of development of early digital gangrene following AV fistula in a patient on maintenance hemodialysis.

Rhinocerebral Mucormycosis in Patients with Kidney Disease Following Covid 19 Infection.

Opportunistic infections saw a rise during the COVID-19 pandemic. We report rhinocerebral mucormycosis following COVID infection in six patients with kidney disease. Though there was a variable outcome with 50% mortality, it is prudent to assess the risk factors for development of life-threatening infection.

Capacity for the management of kidney failure in the International Society of Nephrology South Asia region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The South Asia region is facing a high burden of chronic kidney disease (CKD) with limited health resources and low expenditure on health care. In addition to the burden of CKD and kidney failure from traditional risk factors, CKD of unknown etiologies from India and Sri Lanka compounds the challenges of optimal management of CKD in the region. From the third edition of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we present the status of CKD burden, infrastructure, funding, resources, and health care personnel using the World Health Organization's building blocks for health systems in the ISN South Asia region. The poor status of the public health care system and low health care expenditure resulted in high out-of-pocket expenditures for people with kidney disease, which further compounded the situation. There is insufficient country capacity across the region to provide kidney replacement therapies to cover the burden. The infrastructure was also not uniformly distributed among the countries in the region. There were no chronic hemodialysis centers in Afghanistan, and peritoneal dialysis services were only available in Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Kidney transplantation was not available in Afghanistan, Bhutan, and Maldives. Conservative kidney management was reported as available in 63% (n = 5) of the countries, yet no country reported availability of the core CKM care components. There was a high hospitalization rate and early mortality because of inadequate kidney care. The lack of national registries and actual disease burden estimates reported in the region prevent policymakers' attention to CKD as an important cause of morbidity and mortality. Data from the 2023 ISN-GKHA, although with some limitations, may be used for advocacy and improving CKD care in the region.

An unusual case of reversible acute kidney injury due to chlorine dioxide poisoning.

Chlorine dioxide is a commonly used water disinfectant. Toxicity of chlorine dioxide and its metabolites is rare. In experimental studies, it was shown that acute and chronic toxicity were associated with insignificant hematological changes. Acute kidney injury due to chlorine dioxide was not reported. Two cases of renal toxicity due to its metabolites, chlorate and chlorite were reported. Herein, we report a case of chlorine dioxide poisoning presenting with acute kidney injury.

Assessment of Depression and Its Correlation with Serum Levels of Interleukin-6 in Patients on Maintenance Hemodialysis.

Depression is the most common psychiatric disorder in patients on hemodialysis. An imbalance between proinflammatory and anti-inflammatory cytokines is thought to play a role in the pathogenesis of depression in patients on dialysis. We undertook this study to assess the correlations of the proinflammatory cytokine interleukin 6 (IL-6) and the anti-inflammatory cytokine IL-10 with depression in patients on maintenance hemodialysis. This cross-sectional observational study was carried out at our hospital, a tertiary care referral government teaching hospital, over 2 years. Depression was assessed using the Becks Depression Inventory score. A higher cutoff of >16 was taken for a diagnosis of depression. Clinical, demographic, and laboratory parameters were analyzed. Cytokines were assessed using enzyme-linked immunosorbent assays. Eighty patients satisfied the inclusion criteria. The prevalence of depression in our study was 41.5%. Depression was more common in those who were unemployed and/or illiterate. Mild depression was found in patients from the upper-lower and lower-middle classes, but severe depression was seen in lower-economic classes. Serum levels of IL-6 showed a positive correlation with the severity of depression. Depression was common in patients on maintenance hemodialysis. High levels of serum IL-6 were observed in those with depression. Depression in patients on maintenance hemodialysis is associated with a considerable risk of mortality.

Epidemiology and Outcomes of Glomerular Diseases in Low- and Middle-Income Countries.

Glomerular diseases account for a significant proportion of chronic kidney disease in low-income and middle-income countries (LMICs). The epidemiology of glomerulonephritis is characterized inadequately in LMICs, largely owing to unavailable nephropathology services or uncertainty of the safety of the kidney biopsy procedure. In contrast to high-income countries where IgA nephropathy is the dominant primary glomerular disease, focal segmental glomerulosclerosis is common in large populations across Latin America, Africa, Middle East, and South East Asia, while IgA nephropathy is common in Chinese populations. Despite having a high prevalence of known genetic and viral risk factors that trigger focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis also is common in adults and children in some African countries. Treatment of glomerular diseases in adults and children in LMICs largely is dependent on corticosteroids in combination with other immunosuppressive therapy, which often is cyclophosphamide because of its ready availability and low cost of treatment, despite significant adverse effects. Partial and/or complete remission status reported from studies of glomerular disease subtypes vary across LMIC regions, with high rates of kidney failure, mortality, and disease, and treatment complications often reported. Improving the availability of nephropathology services and ensuring availability of specific therapies are key measures to improving glomerular disease outcomes in LMICs.

Transplant: The Success of Renal Transplant Programs.

In the absence of malignancy or other severe comorbidity, kidney transplantation offers better survival rates and quality of life than dialysis. Despite this survival advantage, many lower- and upper-middle-income countries do not offer adequate kidney transplant services. This is particularly troubling because end-stage kidney disease often is more common in these countries than in high-income countries and overall is less costly in the life of a patient. We describe the contrasting levels of provision of kidney transplantation in Mexico, India, Nigeria, Ghana, and Zimbabwe, and kidney transplant services for children in Africa.

Clinical features and outcomes of 84 COVID-Positive hemodialysis patients in a resource poor setting from India.

With the declaration of severe acute respiratory syndrome novel coronavirus-2019 as pandemic by the World Health Organization on March 11, 2020, there has been a steady rise in number of cases. Chronic kidney disease and dialysis population are risk factors for increased severity of illness. Literature about the coronavirus disease 2019 (COVID-19) in dialysis population is scarce. Management of COVID-19 patients in resource poor setting in a developing country does vary compared to developed nations. Nonavailability of the advanced laboratory facility and the newer medicines forces the treating team to manage the patients with available investigations and drugs. We aimed at analysis of clinical characteristics and outcomes of 84 patients on maintenance hemodialysis (HD). Data of all COVID-positive patients on maintenance HD, who were referred to our center were collected. All patients were given HD on NIKISSO machines. Outcomes of all the admitted patients were analyzed. Maintenance HD group formed majority of the kidney referrals (54%). Age group that was commonly affected was >50 years. Factors associated with mortality were age, diabetes, thrombocytopenia, prolonged baseline activated partial thromboplastin time, admission hypoxemia, high qSOFA score. Institutional Ethics Committee approval has been obtained for the study. Methodology of the study was in accordance with the Declaration of Helsinki. Verbal consent was obtained from patients/ attendants. In the ongoing COVID pandemic, in a developing nation where resources are constrained, it is difficult to salvage the critically ill patients. With the drugs available and the changing strategies, treatment was given to all the patients admitted with bedside renal replacement therapies. Our mortality rate was high compared to other studies due to delay in referral, admission hypoxemia, and late initiation of steroids.

Coronavirus disease 2019 and pregnancy-related acute kidney injury: Our initial experience of six cases.

Pregnancy is identified as one of the risk factors for increased severity of illness in severe acute respiratory syndrome novel coronavirus 2019 infection. The severity of illness may range from mild infection to severe multi-organ failure. Acute kidney injury (AKI) may occur in pregnant patients with coronavirus disease (COVID) either due to obstetric cause or due to severe COVID illness. We report six cases of COVID-pregnancy with AKI and their outcomes.

Assessment of cognitive impairment and its correlation with vitamin D levels patients on maintenance hemodialysis.

Cognitive impairment (CI) is common in patients with chronic kidney disease, and its prevalence increases in patients on hemodialysis (HD). Different factors were identified to be the cause of cognitive dysfunction, of which Vitamin D, which is known to have pleiotropic effects, has been implicated for the neurocognitive decline of functions. We assessed the prevalence of cognitive dysfunction in patients on HD in our center and also studied the deficiency of Vitamin D on CI.

Legal policies of organ transplantation in India: Basics and beyond.

The Organ Transplantation Act issued by the Government of India 1994 has undergone major and minor changes in the form of addition of rules and amendments in order to improve the Act to make it much acceptable legally. Over a period of time, with an increase in cadaver organ donations, the rules and policies with regard to the same have been defined and redefined over the years. In this article, the Act, the rules, the amendments, the quick essentials of approach, and the forms are reviewed.

Noninvasive method of differentiating diabetic nephropathy and nondiabetic renal disease using serum bone morphogenetic protein-7 and transforming growth factor-beta 1 levels in patients with type-2 diabetes mellitus.

Diabetic nephropathy (DN), one of the major complications of diabetes mellitus, is diagnosed by the presence of pedal edema, 24-h proteinuria >300 mg/day, and retinopathy. However, in view of variable clinical presentations and deviation from the above-said clinical features, it has become difficult to diagnose DN or the presence of nondiabetic renal disease (NDRD). Many biomarkers have been identified which could predict the progression of DN. Despite such advancement in science, it is still difficult to differentiate between DN and NDRD. Diabetes is a state of chronic inflammation. Among the pro-inflammatory cytokines, it has been shown that transforming growth factor-beta (TGF-ß) and bone morphogenetic protein-7 (BMP-7) play a key role in the development and progression of DN. We assessed whether the levels of serum BMP-7 and TGF-ß can help differentiate between DN and NDRD, thus serving as surrogate markers of DN.

An unusual clinical presentation of tuberculous pyomyositis in a renal allograft recipient.

We present a renal allograft recipient with pulmonary tuberculosis presenting with multiple subcutaneous abscesses involving left forearm, left thigh, suture site and left loin, which on later evaluation revealed to be due to Mycobacterium tuberculosis.

Isolated Vascular Lesions (IVL) in Early Allograft Biopsies: A Case Series.

This case series includes five patients diagnosed as isolated vascular lesion (IVL) on allograft biopsy in an early post-transplant period. These patients presented with graft dysfunction. The biopsies satisfied the criteria for IVL as laid down by Banff 2009. Four of these patients were treated with corticosteroids and other anti rejection measures. C4d and DSA were negative in all. The patients showed good response to treatment with stable graft function at the longest follow-up of one year. We have also reviewed the literature about IVL as a specific entity. There are differences between the molecular and clinical data of IVL. It is difficult to differentiate whether IVL is a rejection or non-rejection process. This study aims to highlight the importance of a rare entity.

A study of clinical assessment of frailty in patients on maintenance hemodialysis supported by cashless government scheme.

This is a prospective cohort study to assess the prevalence of frailty in patients undergoing maintenance hemodialysis (HD) under the government-funded scheme at our center and to assess the relationship between frailty and falls, hospitalizations, and mortality. This was done at our center which is completely supported by the government, which provides HD to all the patients under poverty line. Epidemiological data, anthropometric measurements, comorbidities assessment, frailty assessment using Fried criteria, subsequent hospitalizations, falls, and mortality were recorded in our prevalent dialysis population at our center between October 2014 and October 2015. Two hundred and twenty-six patients were enrolled during this period. Twenty-one patients were excluded as they did not satisfy the inclusion criteria. Two hundred and five prospective patients were studied for the predictors of frailty. Frailty was present in 82% of the study population. Mean age of our study population was 44.95 ± 13.27 years. On univariate analysis, diabetes mellitus, hypertension (HTN), cerebrovascular accident (CVA), left ventricular dysfunction (LVD), peripheral vascular disease (PVD), smoking, hepatitis C, inadequate dialysis, intradialytic hypotension (IDH), interdialytic weight gain, low serum creatinine <4 mg/dL, and anemia (Hb <10 g/dL) were found to be statistically significantly different between frail and nonfrail groups On multivariate regression analysis, only HTN, PVD, CVA, anemia, smoking, and IDH were found to be significant. Frailty is highly prevalent among dialysis population. Factors predicting frailty include HTN, smoking, LVD, PVD, CVA, smoking, anemia, and IDH. Frailty is a significant risk factor for falls and hospitalizations.

An unusual cause of hematuria following coronary intervention.

Acute renal infarction is rare. Its true incidence is not known. The paucity of literature and unawareness among the physicians makes it an underdiagnosed entity. Herein, we report a case of renal infarction following coronary intervention.

An unusual case of insecticide poisoning presenting as acute kidney injury.

Poisoning due to insecticides such as organophosphorus and super vasmol presenting as acute kidney injury (AKI) is well-reported. Poisoning due to fipronil (phenylpyrazole) is known to present with mild neurological and dermatological complaints. However, fipronil poisoning presenting as AKI and hepatic dysfunction is not known. Herein, we are presenting a case of fipronil poisoning presenting with severe AKI.