Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study.

BACKGROUND: Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India. METHODS: The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases (n = 60) were compared with CKD (n = 62) and healthy subjects (n = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test. RESULTS: CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3-132.7) µg/L compared to CKD 4.5 (0.0-58.8) µg/L and healthy subjects 39.01 (4.8-67.4) µg/L (p < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003-1.024) P < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu (p > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects (P = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029-9.818) p < .05). CONCLUSION: The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.

Unusual Manifestation of Mercuric Chloride Poisoning as Intratubular Nephrocalcinosis - A Rare Case Report.

Mercuric chloride salts are highly toxic compounds that have been linked to suicidal or accidental poisoning. Because of their high solubility, mercuric chloride salts can cause acute tubular injury, corrosive effects in the gastrointestinal system, hematemesis and hematochezia, circulatory collapse, and death. Here, we report an unusual case of mercuric chloride poisoning in a 17-year-old girl who manifested with acute tubular necrosis in association with intratubular nephrocalcinosis and emphasize the role of hemodialysis in the patient's successful recovery.

Takayasu Arteritis in the Pre-Pulseless Phase Presenting as Pyrexia of Unknown Origin.

Pyrexia of unknown origin (PUO) or fever of unknown origin (FUO) is clinically challenging for a treating physician; it is also a conundrum for the patient until a definitive diagnosis is made. Despite extensive investigations, many cases of PUO may remain undiagnosed for a long time. In a resource-limited country like India, due to the limited availability of various diagnostic tests, a great many fever cases are classified as PUO. Here, we present a case report of Takayasu arteritis in its pre-pulseless phase, presented as PUO. Takayasu arteritis presenting as PUO in the absence of a pulse deficit is uncommon and rarely reported. The patient's fever responded to steroids with methotrexate. The patient didn't develop any vascular complications during the follow-up.

Melioidosis as a Mystique Infection: A Study From Central India.

INTRODUCTION: Melioidosis is caused by the Gram-negative bacilli Burkholderia pseudomallei, which is found in contaminated water and soil and spreads via inhalation, inoculation, and ingestion. Melioidosis manifests diversely in immunocompetent and immunocompromised patients, ranging from asymptomatic to life-threatening respiratory distress, septic shock, localized tissue infection, necrotizing pneumonia, and soft organ abscesses.  Methods: An 18-month observational study was conducted at a tertiary center in central India among various confirmed melioidosis cases, with data gathered and analyzed. Aerobic culture and sensitivity were performed in all studied cases, either in blood/body fluid/localized collection - using blood agar media for the culture and disc diffusion method on Mueller Hinton agar for sensitivity. Other tests, such as radiological imaging, were conducted according to symptoms and signs of localized infection. RESULTS: The melioidosis cases under study were compared on various clinical/presenting parameters. Melioidosis has a variety of risk factors, but we found that, in India, diabetic patients are at a higher risk of this infection, particularly fatal forms, as all of the patients in our study were diabetic. Melioidosis is known to have joint involvement, either as a source of infection or later in the course of the disease. All cases were successfully treated with antibiotics and surgical procedures, demonstrating the significance of determining disease etiology, early diagnosis, and rapid early management. CONCLUSION:  Melioidosis is a potentially fatal disease, particularly in diabetics, with a wide range of symptoms and complications. Physicians face a variety of challenges, including clinical symptoms resembling other chronic illnesses, such as tuberculosis, delays in laboratory confirmation, underdiagnosis, reduced reporting, and a lack of suspicion. Because there are very little data and it is a seldom reported infection from central India, we are publishing a study on seven melioidosis patients.

Obstructive sleep apnea and ambulatory blood pressure abnormalities in children with chronic kidney disease.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common complications in children with chronic kidney disease (CKD). Progression of CKD can aggravate OSA and hypertension whereas worsening sleep apnea can make hypertension difficult to treat in CKD patients. We, therefore, conducted a prospective study to evaluate the association between OSA and hypertension in pediatric patients with CKD. METHOD: In this prospective observational study consecutive children with CKD stage 3-5 (nondialysis dependent) underwent overnight polysomnography and 24-h ambulatory blood pressure monitoring (ABPM). The detailed clinical features and investigations were recorded in a prestructured performa. RESULTS: Twenty-two children completed overnight polysomnography and 24-h ABPM was performed within 48 h of performing polysomnography. The median (IQR) age of the study population was 11 (8.5-15.5) years, with an age range of 5-18 years. Moderate-severe OSA defined as apnea-hypopnea index (AHI ≥5) was seen in 14 (63.6%) children, periodic limb movement syndrome in 20 (91%) and poor sleep efficacy in 9 (40.9%) children. Ambulatory blood pressure was abnormal in 15 (68.2%) children with CKD. Of them, 4 (18.2%) had ambulatory hypertension, 9 (40.9%) had severe ambulatory hypertension and 2 (9.1%) had masked hypertension. A statistically significant correlation of sleep efficiency with nighttime DBP SD score/Z score (SDS/Z) (r = -0.47; P = 0.02); estimated glomerular filtration rate with SBP loads (r = -0.61; P < 0.012); DBP loads (r = -0.63; P < ) and BMI with SBP load (r = 0.46; P = 0.012) was found. CONCLUSION: Our preliminary findings suggest that ambulatory blood pressure abnormalities, OSA, periodic limb movement syndrome and poor sleep efficiency are highly prevalent in children with CKD stages 3-5.

Hypertriglyceridemia with pancreatitis at disease onset in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the presence of several autoantibodies, immune complex formation and multiple organ system involvement. SLE has a wide range of manifestations involving nearly all organ systems. Hypertriglyceridemia (HTG) in SLE is a well-established and a common abnormality, which is generally mild and not included in the diagnostic criteria of SLE. HTG as the initial manifestation of SLE in adult patients in association with acute pancreatitis at levels below 1000 mg/dL has not been previously reported. Here, we report a case of rare presentation of moderate HTG (TG-869 mg/dL) with pancreatitis at disease onset in an adult women which later proved to be due to SLE and progressed to levels of severe HTG during the course of illness. The patient was successfully treated with plasma exchanges and cyclophosphamide.

Association of Single Nucleotide Polymorphisms in KCNA10 and SLC13A3 Genes with the Susceptibility to Chronic Kidney Disease of Unknown Etiology in Central Indian Patients.

Global rise in the prevalence of endemic chronic kidney disease of unknown etiology (CKDu) possess major health issues. The prevalence of CKDu is also rising in the Indian population. Besides environmental factors, genetic factors play an important role in the predisposition to CKDu. In the present study, we have analyzed the association of single nucleotide polymorphisms (SNPs) in three genes with the susceptibility to CKDu. This was a case-control study with a total of 180 adult subjects (CKD = 60, CKDu = 60, Healthy = 60) from central India. We performed KASP genotyping assay to determine the allele frequency of SNP genotypes. We used the odds ratio (OR) to assess the association of individual SNPs, rs34970857 of KCNA10, rs6066043 of SLC13A3, and rs2910164 of miR-146a with CKDu and CKD susceptibility. In the case of rs34970857 of the KCNA10 gene, we noted a significantly increased OR for CKDu versus healthy control (Dominant model; CKDu versus control, CT + CC versus TT, OR = 3.96, p = 0.004). In the recessive and homozygous model, we observed significantly increased OR for rs6066043 of SLC13A3 gene, CKDu versus healthy control {(Recessive model; CKDu versus control, GG versus AA + GA, OR = 2.41, p = 0.03; homozygous model, GG versus AA, OR = 3.54, p = 0.04)}. CC genotype of rs34970857 of the KCNA10 gene and the GG genotype of the SLC13A3 gene are significantly associated with the susceptibility of CKDu.

Acute kidney injury following multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis.

INTRODUCTION: Multisystem inflammatory syndrome (MIS-C) is a rare paediatric hyper-inflammatory disorder that occurs following SARS-CoV-2 infection. Acute kidney injury (AKI) occurs in approximately one-quarter to one-third of the patients with MIS-C and is associated with poor prognosis in critically ill children. This systematic review is aimed to evaluate the incidence of AKI, mortality, and the need for kidney replacement therapy (KRT) in patients with MIS-C. METHODS: We searched databases from Medline, EMBASE, Cochrane Register, and Google Scholar from December 2019 to December 2021 with our search strategy. Studies meeting the following criteria were included in this systematic review: (1) articles on AKI in MIS-C; (2) studies providing AKI in MIS-C and COVID-19 infection separately; (3) studies reporting outcomes such as mortality, KRT, serum creatinine; length of hospital/ICU stay. QUALITY ASSESSMENT: The quality of the included studies was independently assessed by using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool for cohort studies and case series. STATISTICAL ANALYSIS: Outcomes and their 95% confidence intervals (CI) were reported if a meta-analysis of these outcomes was conducted. Heterogeneity was reported using I2 statistics, and heterogeneity ≥ 50% was considered high. We used Baujat's plot for the contribution of each study toward overall heterogeneity. In sensitivity analysis, the summary estimates were assessed by repeating meta-analysis after omitting one study at a time. Forest plots were used for reporting outcomes in each study and with their 95% CI. All statistical tests were performed using R software version 4.0.3. RESULTS: A total of 24 studies were included in this systematic review and of these, 11 were included in the meta-analysis. The pooled proportion of patients with MIS-C developing AKI was 20% (95% CI: 14-28%, I2 = 80%). Pooled proportion of death in children with MIS-C was 4% (95% CI: 1-14%; I2 = 93%). The odds of death in patients with AKI were 4.68 times higher than in patients without AKI (95% CI: 1.06-20.7%; I2 = 17%). The overall pooled proportion of MIS-C-induced AKI patients requiring KRT was 15% (95% CI: 4-42%; I2 = 91%). CONCLUSION: Approximately one-fifth of children with MIS-C develop AKI which is associated with higher odds of death. PROSPERO registration: CRD42022306170 A higher resolution version of the Graphical abstract is available as Supplementary information.

Potential Association of Hypernatremia With Mortality in Patients With Acute Kidney Injury and COVID-19.

Background The outcome of acute kidney injury (AKI) in patients with COVID-19 and the factors associated with its outcome, including mortality, are understudied among the Indian population. Objective The objective of this study is to determine the outcome of AKI in a cohort of patients with COVID-19 admitted to medical wards and associated intensive care unit (ICU) and the factors associated with its outcome, including mortality. Method This is a retrospective study of patients with COVID-19 and AKI admitted to a tertiary care hospital. A total of 1765 patients were admitted to a hospital with COVID-19 between March 23, 2021, and June 30, 2021, during the second wave of the pandemic chiefly attributed to SARS-Co-V-2 lineage B.1.617. Patients with AKI for whom a nephrology call was sought for management (N=60) were included. Measurements carried out were the stage of AKI, co-morbidities, ICU admission, mechanical ventilation, lab parameters, and mortality. We classified AKI by comparing the highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We further developed stepwise logistic regression models to find independent factors associated with mortality.  Results Out of the 1765 patients hospitalized with COVID-19, a total of 60 (3.4%) patients with AKI were referred to nephrology for management. The observed mortality in this cohort was 41/60 (68.3%). AKI stage 3 was observed to be the most common (78.3%). Based on a univariate analysis of association, age, chronic kidney disease, admission to ICU, the requirement for vasopressor and ventilation, lactate dehydrogenase (LDH) DH, liver function tests (LFT), hypernatremia, and leucocytosis were associated with the mortality of patients (p<0.05) with AKI and COVID-19 infection. Multivariate analysis using logistic regression led to the identification of hypernatremia (OR 5.24 {0.95-42.31}) and multiple co-morbidities (OR 2.59 {1.03-8.75}, p<0.07) as potential factors independently associated with mortality. Conclusion The study indicates the potential association of hypernatremia with mortality in AKI, along with the simultaneous presence of multiple co-morbidities with COVID-19. As the statistical power of the association is weak, we are claiming the association as potential only. It needs to be confirmed in other larger studies.

Outcomes following peritoneal dialysis for COVID-19-induced AKI: A literature review.

Acute kidney injury (AKI) has been shown to be associated with significant morbidity and mortality in patients with severe COVID-19 disease. Due to increasing number of cases in pandemic, there is a significant shortage of medical facilities and equipment in relation to patient load. In low resource settings where access to intermittent haemodialysis (HD) or continuous kidney replacement therapy (CKRT) is limited, peritoneal dialysis (PD) may play a vital role in the management of COVID-19-induced AKI. A literature search using Medline/PubMed, Embase, Google Scholar and Cochrane register was performed using following search strategy: (((COVID 19) OR (SARS-CoV-2)) AND (((acute kidney injury) OR (acute renal failure)) OR (acute renal dysfunction))) AND (peritoneal dialysis). Search strategy yielded total 79 articles. After going through titles and abstracts, full text of 15 articles was obtained. Finally, six studies were included in the review after exclusion of 10 studies. Five studies were single centre and one study was multicentric; four studies were conducted in the United States and one in the United Kingdom; PD catheter placement was done by surgeons in three studies and by nephrologist in one study. The mortality reported in the studies varied from 43% to as high as 63%.

Immune Complex Associated Glomerulonephritis in a Patient with Prefibrotic Primary Myelofibrosis: A Case Report.

A case of prefibrotic myelofibrosis with immune complex-mediated glomerulonephritis is presented. A 45-year-old female, with history of right subclavian and axillary vein thrombosis, presented with abdominal distension, facial puffiness, and pedal edema. Evaluation revealed deranged renal functions with nephrotic range proteinuria and acute kidney injury. JAK2 mutation evaluated in view of portal vein thrombosis and splenomegaly was positive. Renal biopsy revealed mesangial proliferative glomerulonephritis with full house immune complex deposition on direct immunofluorescence (DIF). The patient had no signs or symptoms of systemic lupus erythematosus and serological markers for autoimmune or collagen vascular disease were negative. Renal involvement in myeloproliferative neoplasms (MPNs) is uncommon and histological patterns of DIF negative mesangial proliferative glomerulonephritis, focal segmental glomerulosclerosis, and immunoglobulin A nephropathy have been reported.

Type-5 Bartter syndrome presenting with metabolic seizure in adulthood.

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter's syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

Nephrocalcinosis-A gateway to the Diagnosis.

Nephrocalcinosis (NC) is the augmented calcium content within the renal parenchyma. Its pathogenesis mainly involves hypercalciuria. The presence of medullary NC provides a window to the clinician for the diagnosis of many important diseases. In this case series, we highlight three diseases that could be diagnosed with a high index of suspicion and detailed evaluation after their presentation as medullary NC.

Antipsychotics and hemodialysis: A systematic review.

OBJECTIVE: Antipsychotics play a crucial role in the management of behavioral problems in patients undergoing hemodialysis. Oral and injectable antipsychotics are routinely prescribed to control emergent delirium or exacerbation of previous psychiatric symptoms. However scanty literature is available on the pharmacokinetics of antipsychotics in such patients. Avoiding amisulpride and warning against increasing the dosage in renal failure is the only recommendation by drug manufacturers and clinical guidelines. Hemodialysis affects the volume of distribution (Vd) and blood levels of antipsychotics in a complex manner. It is hence difficult to equate data on renal failure with hemodialysis to reliably predict the treatment response. METHOD: We systematically analyzed online data from 1981 to 2019 on the use of antipsychotics in hemodialysis. The outcome was defined as the safety and efficacy of AP, measured in terms of adverse effects and relapse of existing or new onset of behavioral symptoms in Hemodialysis. RESULTS: The data from 182 studies revealed that only 14 case reports and 1 case series met the review criteria. Oral Risperidone, Clozapine, Aripiprazole, Ziprasidone, Haloperidol, and Long-acting Risperidone, Flupenthixol, and Paliperidone were the antipsychotics studied in terms of pharmacokinetics during hemodialysis. AP levels in the blood were found to be unaffected in two studies during HD while the other two studies recommended scheduling of AP regimen w.r.t HD session. Six reports mentioned exacerbation of pre-existing psychiatric ailments in patients undergoing HD, the most common being schizophrenia. CONCLUSION: Findings of the review reveals modest evidence favoring multiple dosing regimens of oral aripiprazole, ziprasidone, olanzapine, and risperidone. Long-acting risperidone and paliperidone are well tolerated and half of the conventional dose may be effective in the case of paliperidone. Though CYP-3A4 remains relatively and transiently unaltered during hemodialysis, none of the antipsychotics are compromised in HD. While selecting an AP during HD, one has to consider the protein binding, clearance by dialysis, duration of an HD session, route of administration of AP, and impaired bowel absorption in HD.

Basiliximab induction in renal transplantation: long-term outcome.

Anti-IL-2 receptor has been proven to be effective in reducing the rate of acute rejection in kidney transplantation and also in improving the graft and patient survival rates. In this study, we retrospectively reviewed the role of the anti-IL-2 receptor, basiliximab, as an induction immunosuppression. Fifty-seven kidney transplant recipients from living donors who received the IL-2 blocker basiliximab (Group 1) as induction therapy in combination with cyclosporine (CsA), steroids and mycophenolate mofetil (MMF) or azathioprine (AZA) were compared with similarly matched renal transplant recipients (N = 312) who did not receive induction therapy (Group 2). Survival analysis was performed using the Kaplan-Meir method. Chi-square test was used to compare the outcome difference of various parameters between the two groups. Both the groups were similar in terms of demographic characteristcs and maintenance immunosuppression used. The total number of rejections was significantly less in Group 1, 14% vs 25% in Group 2 (P = 0.04, Odds ratio = 0.44). A higher number of patients in Group 2 had steroid-resistant rejections, although the difference was not statistically significant (9.9% in Group 2 vs 5.3% in Group 1). Death-censored graft survival was not significantly better in Group 1 at five years as compared with Group 2 (79.4% vs 47.2%, P = 0.09). On multivariate analysis for association with graft survival, only late acute rejections and steroid-resistant rejections were independently associated with poor graft survival, while the type of maintenance immuno-suppression (MMF vs AZA), use of basiliximab induction therapy and total number of acute rejection episodes had no association. Our study suggests that the use of anti-IL-2 receptor antibody basiliximab as induction immuno-suppression results in significantly better prevention of acute rejection, but it does not result in a significantly improved graft survival at five years. It also results in reduced severity of acute rejection.