Transit time estimation of drying springs in Uttarakhand region using environmental tritium concentration.

Many parts of the Uttarakhand state, situated in the hilly terrain of the Himalayan region of India are facing acute water crisis due to the drying up of the perennial springs which are the only source of potable water in those regions. Tritium (3H), the radioactive isotope of hydrogen (half-life of 12.32 years) and also a part of water molecule (in the form of HTO) acts as a very useful tracer in estimating the transit time of the hydrological systems. Tritium concentrations of three springs (S-1, S-2 and S-3) were monitored consecutively for three years (2017-2019) to better constrain the transit time estimation. The tritium concentrations of the springs are found to vary between 3.66 and 4.15 TU. All the springs show gradual decrease in tritium concentration with the passage of time indicating the diminishing percentage of freshly recharged modern water component. Among various lumped parameter models, the piston-flow model (PFM), exponential mixing model (EMM), exponential piston-flow model (EPM) and partial exponential mixing model (PEM) have been employed in this study. The historical record of weighted mean concentration of tritium in precipitation available for the Uttarakhand region is taken as input function in the modelling procedure. The application of various LPMs (PFM, EMM, EPM and PEM) indicates that the transit time of the S-1 spring ranges from 1.26 to 1.46 years whereas for S-2 spring, the transit time is found to vary from 5 months to 1.1 years. The MTT of S-3 spring ranges from 5 months to 11 months. The relatively short residence time of these springs indicates the actively recharged system. The estimation of accurate transit time is thus very crucial for understanding the renewability of the spring water systems.

Anti-glomerular basement membrane disease: Treatment outcome of cyclophosphamide vs. rituximab induction therapy regimen.

AIM: To study the clinical profile of anti-glomerular basement membrane (anti-GBM) disease and its outcome with two different treatment regimens comprising either cyclophosphamide (CYC) or rituximab (RTX). MATERIALS AND METHODS: A retrospective analysis of anti-GBM crescentic glomerulonephritis patients admitted to our hospital over 5 years. RESULTS: 14 patients were diagnosed with anti-GBM crescentic glomerulonephritis. The mean duration of symptoms was 3.6 ± 1.9 weeks. All patients presented with rapidly progressive glomerulonephritis (RPGN). Five (35.7%) patients had concomitant urinary tract infection (UTI), 2 (14.3% had underlying type 2 diabetes mellitus, 5 (35.7%) patients also had positive anti-neutrophil cytoplasmic antibodies (ANCA), and 9 (64.3%) were dialysis-dependent at presentation. Four (28.6%) patients developed diffuse alveolar hemorrhage (DAH). All patients received baseline corticosteroids, and 7 (50%) patients also received plasmapheresis. Nine (64.3%) patients were treated with CYC, and 3 (21.4%) patients received RTX. In the CYC arm, 2 (28.6%) patients died, 3 had end-stage kidney disease (ESKD) at 3 months, and 2 had chronic kidney disease (CKD) stage III at 3 months of follow-up. Two patients were lost to follow-up. In the RTX arm, all 3 patients survived with no incidence of DAH, 1 patient each had ESKD and CKD stage III, and 1 dialysis-dependent patient achieved normal kidney function at the end of 3 months. CONCLUSION: Most patients presented late with dialysis-dependent renal failure, and many had concomitant UTI. Concomitant infection causes diagnostic confusion with RPGN and DAH, which delays diagnosis and treatment. RTX as an alternative to CYC in addition to baseline corticosteroids and/or plasmapheresis and is associated with favorable outcomes.

Retino-Renal Dissociation in Type 2 Diabetes Mellitus: An Observational Cross Sectional Study at a Tertiary Care Center of Sub-Himalayan Region.

INTRODUCTION: Diabetic retinopathy, the diabetes-specific long-term microvascular complication is an important predictor of diabetic nephropathy. Diabetes induced retinopathy mostly proceeds nephropathy in patients with Type1 diabetes; however, this sequence is not consistent in patients with Type 2 diabetes and has significant discordance. METHODS: It was a hospital-based prospective, observational study conducted at Indira Gandhi Medical College, Shimla Himachal Pradesh a tertiary care center in the sub-Himalayan region of India from July 2016 to June 2017. A total of 141 patients were recruited in this study period. RESULTS: 141 patients with type 2 diabetes, 83(58.9%) males,58(41.1%) females were recruited in the study. The mean duration of diabetes in this study was 5.78±6.21 years. Mean HbA1C in our study was 9.66±3.04%. 79(56.0%) patients in our study had HbA1C more than 9.0% while 39(27.7%) had HbA1C between 7.0- 9.0%. only 23 (16.3%) patients had HbA1C less than 7.0%. A total of 118 (83.7%) patients had poor glycaemic control. Out of a total of 141 patients, DKD (albuminuria and/or reduced eGFR) was present in 67 (47.52%) patients. 33 had diabetic retinopathy. CONCLUSION: The relationship between retinopathy and nephropathy in type 2 diabetic patients is not as clear as in type 1 diabetic patients. Patients with type 2 diabetes do not have diabetic nephropathy always and non-diabetic renal disease is also quite common. The absence of retinopathy, rapid progression diabetes, presence of RBC, and cast are some of the atypical findings, and patients presenting with them should be subjected to renal biopsy to rule out non-diabetic renal disease (NDRD).

The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics.

BACKGROUND: Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low-middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. METHODS: ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. RESULTS: A total of 4056 patients have been enrolled up to 31 March 2020. The mean ± SD age was 50.3 ± 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73 m2. About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. CONCLUSIONS: The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.

Renin-angiotensin blocker use is associated with improved cardiovascular mortality in Indian patients with mild-moderate chronic kidney disease-findings from the ICKD study.

Introduction: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are the antihypertensive drug class of choice in patients with chronic kidney disease (CKD). Head-to-head comparisons of the renal or non-renal outcomes between ACEI/ARB users and nonusers have not been conducted in all population groups. We examined the renal and cardiovascular outcomes in users and nonusers enrolled in the Indian Chronic Kidney Disease (ICKD) Study. Methods: A total of 4,056 patients with mild-moderate CKD were studied. Patients were categorized as ACEI/ARB users or nonusers. Major adverse kidney events [ESKD (end stage kidney disease), ≥50% decline in eGFR and kidney death], all-cause mortality, and cardiovascular mortality were analyzed over a median follow-up period of 2.64 (1.40, 3.89) years between the two groups. Results: Out of a total of 4,056 patients, 3,487 (87%) were hypertensive. The adjusted sub-hazard ratio (SHR) and 95 % CI for ACEI /ARB users was 0.85 (0.71, 1.02) for MAKE, 0.80 (0.64, 0.99) for a 50% decline in eGFR, and 0.72 (0.58, 0.90) for ESKD. For cardiovascular mortality, ACEI/ARB users were at lower risk (SHR = 0.55, 95% CI: 0.34, 0.88). Diuretic users were at increased risk of all-cause mortality (HR = 1.95, 95% CI: 1.50, 2.53) and cardiovascular mortality (adjusted SHR = 1.73, 95% CI: 1.09, 2.73). There was non-significant association between the use of other antihypertensives and any of the end points. Discussion: ACEI/ARB use is associated with slower rate of decline in eGFR in those with CKD stage 1-3. ACEI/ARB users had a significantly lower risk of renal outcomes, and cardiovascular mortality.

Epidemiology and outcomes of dialysis requiring acute kidney injury: A single-center study.

OBJECTIVES: Acute kidney injury (AKI) is a common diagnosis in hospitalized patients. Dialysis requiring AKI (AKI-D) is associated with adverse outcomes. This study aims to know the clinical profile and short-term outcomes at 3 months, in patients with AKI-D, at our center. METHODS: A prospective observational study was done of all the patients admitted with AKI-D for 2 years, from July 2018 to June 2020. We recorded clinical parameters at baseline and postdischarge follow-up at 3 months. RESULTS: One hundred twenty-eight patients had AKI-D over 2 years. Then, 116 (90.6%) patients had community-acquired AKI (CAAKI), and 12 (9.4%) patients had hospital-acquired AKI. The underlying causes of AKI-D were: toxins in 48 (37.5%), sepsis in 31 (24.2%), acute kidney disease in 15 (11.7%), acute gastroenteritis (AGE) in 9 (7%), and cardiogenic shock in 7 (5.5%) patients. The mean values of intact parathyroid hormone (available in 32% of patients) were 268 pg/mL. Intermittent hemodialysis was the commonest mode of dialysis (85.2%). A kidney biopsy was done in 23 (18%) patients. The most common diagnosis on kidney biopsy was glomerulonephritis (GN) in 12 patients (crescentic GN-9 and IgA nephropathy-3), followed by acute tubule-interstitial nephritis in 6 patients. In-hospital mortality was 29.7%. Overall, 39% regained serum creatinine in the normal range at 3 months, 36.7% died, 14.1% reached chronic kidney disease (CKD), 7.8% lost to follow-up, and 2.3% had reached end-stage renal disease. CONCLUSION: The majority of AKI-D at our center was CAAKI. A significant chunk of AKI-D (68.7%) was caused by preventable causes like toxins, sepsis, and AGE. Dysregulation of mineral metabolism was conspicuous. In chemical toxin vs. biological toxins and undifferentiated sepsis vs. the identifiable cause of sepsis, formers had significantly more in-hospital mortality than the latter ones. AKI-D is associated with high in-hospital mortality, total mortality, and risk of progression to CKD at 3 months.

Unravelling 30 ka recharge history of an intensely exploited multi-tier aquifer system in North West India through isotopic tracers - Implications on deep groundwater sustainability.

Northwest part of India is an agriculturally active region experiencing rapid rise in food production and steep decline in groundwater levels. The freshwater requirement is mostly met by regional aquifers which are inherently heterogeneous and undergoing extensive human inducted perturbations. These factors pose great challenge in planning sustainable groundwater management. In this study, environmental isotopes (2H, 18O, 13C, 3H and 14C) were applied to understand the regional recharge mechanism during the last 30 ka and hydrogeological controls impacting the aquifer dynamics and inter-aquifer connectivity of the Ghaggar River basin. Rayleigh distillation modeling indicates that major groundwater recharge is through monsoonal rains while rainfall during other seasons is lost either through evaporation or surface runoff. The evaporation loss is estimated to be 1.5 to 10% and more pronounced in the southern part of the study area. Regional recharge from Siwalik foothills contributes to groundwater up to a depth of 250 m below ground level (bgl). The lumped parameter modeling (LPM) using 3H data estimated groundwater ages 34.7 ± 12.1 and 95.8 ± 11.3 years for shallow and deep aquifers respectively. Radiocarbon dating indicates presence of paleogroundwater (0.4 to 28.6 ka before present, BP) in the deeper aquifer of central part of the study area. Interpretation of the paleowater and paleoprecipitation isotope data in conjunction with available paleogeomorphologic information suggests two different recharge phases. Phase I extending from ~28.6 to 10.1 ka, showed ~48-61% contribution from isotopically depleted perennial river system. Phase II spanning from ~12.5 to 0.4 ka BP showed insignificant contribution from river recharge, which can be attributed to the decreased strength of the perennial river flows. The research methodology proposed in this study will be beneficial in improving the understanding of groundwater storage and its variability with changes in regional climatic conditions.

Prescription Practices in Patients With Mild to Moderate CKD in India.

INTRODUCTION: Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD. METHODS: The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use. RESULTS: Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively. CONCLUSION: This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD.

A case report of pleuro-pericardial effusion in a patient on hemodialysis and a cardiac pacemaker.

There are multiple causes of pleuro-pericardial effusion (PPEF) and more so in a patient with end-stage renal disease (ESRD). Postcardiac injury syndrome (PCIS) is a loosely defined term for occurrence of pericardial and/or pleural effusion (PLEF), low-grade fever, with or without systemic upset, which occurs after myocardial infarction (MI), and other cardiac interventions. PPEF is one of its salient manifestations. We report occurrence of PCIS, presenting as pericardial effusion and massive PLEF, after insertion of cardiac pacemaker in a patient with ESRD, on maintenance hemodialysis (MHD). It was successfully managed with a short course of oral steroids.

Fluoride Geochemistry and Exposure Risk Through Groundwater Sources in Northeastern Parts of Rajasthan, India.

Exposure to fluoride concentrations above a threshold of 1.5 mg/L can cause joint pains, restricted mobility, skeletal and dental fluorosis. This study aims to determine the hydrochemical evolution of the fluoride-rich groundwater and estimate the risk of fluoride exposure to the residents of semi-arid northeastern part of Rajasthan, India. The methodology involves measurement of fluoride and other ionic concentrations in groundwater using ion chromatography, followed by an estimation of the cumulative density function and fluorosis risk. The fluoride concentration in water samples varied from 0.04 to 8.2 mg/L with 85% samples falling above the permissible limit. The empirical cumulative density function was used to estimate the percentage and degree of health risks associated with the consumption of F- contaminated water. It is found that 55% of the samples indicate risk of dental fluorosis, 42% indicate risk of deformities to knee and hip bones, and 18% indicate risk of crippling fluorosis. In addition, instances of high nitrate concentrations above the permissible limit of 45 mg/L are also found in 13% of samples. The fluoride rich groundwater is mainly associated with the Na-HCO3-Cl type water facies while low fluoride groundwater shows varied chemical facies. The saturation index values indicate a high probability of a further increase in F- concentration in groundwater of this region. The calculated fluoride exposure risk for the general public in the study area is 3-6 times higher than the allowed limit of 0.05 mg/kg/day. Based on the results of this study, a fluorosis index map was prepared for the study area. The northern and northeastern parts are less prone to fluorosis, whereas the south-central and southwestern parts are highly vulnerable to fluorosis. The inferences from this study help to prioritize the regions that need immediate attention for remediation.

Coronavirus Disease 2019 and the Kidney.

Coronaviruses are ubiquitous pathogens and have caused epidemics in the recent past. Coupled with globalization, they have the potential to transform into the pandemic, as is the case of coronavirus disease 2019 (COVID-19). Primarily to start as a respiratory illness, they are known to cause systemic disease and affect many organ systems. Due to the lack of, universally proven, specific anti-viral therapy, the mainstay of treatment is "supportive care" and some of the patients afflicted with it, require intensive care and organ support for lungs and/or kidneys. Patients with the diseases of the kidney, particularly those on dialysis and kidney transplant recipients, are predisposed to the worst outcomes with COVID-19. It also leads to acute kidney injury, which is an important and independent determinant of prognosis in these patients. It also creates a huge demand for the delivery of renal replacement therapy. COVID-19 is an emerging and evolving disease, and so, it is important to understand the mechanism and management of kidney diseases in COVID-19.

Clinical Profile and Outcome of IgA Nephropathy from a Tertiary Care Hospital in North India.

AIM: To study the clinical profile and outcome of the patients with kidney biopsy diagnosis of IgA Nephropathy (IgAN). METHODS: A retrospective study of the patients diagnosed IgAN over a period of three and half years. RESULTS: Sixty (13.5%) had a diagnosis of IgAN. Twenty four (40%) had a clinical diagnosis of rapidly progressive glomerulonephritis (RPGN), 20 (33.3%) chronic kidney disease (CKD), 11 (18.3%) nephrotic syndrome, three (5%) acute glomerulonephritis and two (3.3%) asymptomatic urinary abnormalities. Fifty-six (93.4%) patients had hypertension; 15 (25%) patients were presenting as a hypertensive crisis with malignant hypertension in two. Fifteen of the RPGN patients presented with the hypertensive crisis, and all of them had evidence of thrombotic microangiopathy (TMA) on biopsy. Three (5%) patients had secondary IgAN. Patients with the nephrotic syndrome responded to treatment and had a significantly higher renal survival. Patients with interstitial fibrosis and tubular atrophy (IFTA) ≥25% and mesangial hypercellularity score of >0.5 did not respond to treatment. CONCLUSION: RPGN, CKD, and nephrotic syndrome were the typical manifestation of IgAN. Hypertension and hypertensive crisis were common. Response to treatment was seen in nephrotic syndrome whereas those with IFTA ≥25% and mesangial hypercellularity score of > 0.5 did not respond to treatment.

Nonmedical Factors and Health-Related Quality of Life in CKD in India.

BACKGROUND AND OBJECTIVES: Patient-reported outcomes have gained prominence in the management of chronic noncommunicable diseases. Measurement of health-related quality of life is being increasingly incorporated into medical decision making and health care delivery processes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Indian Chronic Kidney Disease Study is a prospective cohort of participants with mild to moderate CKD. Baseline health-related quality of life scores, determined by the standardized Kidney Disease Quality of Life 36 item instrument, are presented for the inception cohort (n=2919). Scores are presented on five subscales: mental component summary, physical component summary, burden, effect of kidney disease, and symptom and problems; each is scored 0-100. The associations of socioeconomic and clinical parameters with the five subscale scores and lower quality of life (defined as subscale score <1 SD of the sample mean) were examined. The main socioeconomic factors studied were sex, education, occupation, and income. The key medical factors studied were age, eGFR, diabetes, hypertension, and albuminuria. RESULTS: The mean (SD) subscale scores were physical component summary score, 43±9; mental component summary score, 48±10; burden, 61±33; effects, 87±13; and symptoms, 90±20. Among the socioeconomic variables, women, lower education, and lower income were negatively associated with reduced scores across all subscales. For instance, the respective ß-coefficients (SD) for association with the physical component summary subscale were -2.6 (-3.4 to -1.8), -1.5 (-2.2 to -0.7), and -1.6 (-2.7 to -0.5). Medical factors had inconsistent or no association with subscale scores. The quality of life scores also displayed regional variations. CONCLUSIONS: In this first of its kind analysis from India, predominantly socioeconomic factors were associated with quality of life scores in patients with CKD.

Lentiform fork sign: Uremia alone or multifactorial causation?

Neurological complications are common in patients with acute or chronic renal failure, especially when there is marked reduction in the glomerular filtration rate (GFR). One such clinical syndrome, uremic encephalopathy (UE), occurs due to widespread dysfunction of central nervous system (CNS). It manifests with myriad clinical features and usually is suggested by bedside elicitation of asterixis (flapping tremor). Symptomatic involvement of the basal ganglia manifesting as choreoathetosis and clinical and radiological resolution with hemodialysis has been reported in the medical literature, but only rarely. The present report details such a case.

Mortality due to mass Hymenoptera attacks: A serious but underrecognized public health problem in a mountainous state of India.

Most deaths related to Hymenoptera are a result of immediate hypersensitivity reactions causing anaphylaxis to one or few stings. However, if the patient is exposed to a large quantity of the venom due to mass/multiple stings, massive envenomation can cause death in nonallergic individuals. Thirty-nine cases of acute kidney injury (AKI) who followed mass attacks by Hymenoptera were seen over 15 years, with a reference period between 2003 and 2017. AKI was severe; most (85%) of them required dialysis and one-third died. Mass attacks by Hymenoptera have become a serious public health problem in tropics. There is no antivenom, and treatment in such cases is supportive. Early hospitalization is vital to reduce morbidity and mortality.

Epidemiology and outcome of acute kidney injury due to venomous animals from a subtropical region of India.

AIM: To study the epidemiology and outcome of acute kidney injury (AKI) caused by venomous animals. METHODS: A retrospective study of patients admitted at Indira Gandhi Medical College Hospital, Shimla, with AKI due to venomous animals over a period of 15 years (January 2003-December 2017). Medical records were evaluated for patient information on demographic factors, clinical characteristics, complications, and outcome. Outcomes of requirement for intensive care unit (ICU) support, treatment with dialysis, survival, and mortality were analyzed. The survival and non-survival groups were compared to see the difference in the demographic factors, laboratory results, clinical characteristics, and complications. RESULTS: One hundred and eighty-one patients were diagnosed with AKI caused by venomous creatures. Mean age was 44 ± 15.4 years, and the majority (54.1%) was women. Snakebite (77.9%) and wasp stings (19.9%) were the leading causes of AKI. Clinical details were available in 148 patients. The median duration of arrival at hospital was two days. 81.8% had oliguria, and 54.7% had a history of hematuria or having passed red or brown colored urine. The hematological and biochemical laboratory abnormalities were as follows: anemia (75%), leukocytosis (75.7%), hyperkalemia (35.8%), severe metabolic acidosis (46.6%), hepatic dysfunction (54.7%), hemolysis (85.8%), and rhabdomyolysis (65.5%). Main complications were as follows: gastrointestinal bleed (9.5%), seizure/encephalopathy (10.8%), and pneumonia/acute respiratory distress syndrome (ARDS) (11.5%). 82.3% of the patients required dialysis. 154 (85.1%) patient survived, and 27 (14.9%) patients died. As compared to the survival group, the white blood cell count, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, creatine kinase, and lactate dehydrogenase were significantly higher, and serum albumin levels were significantly lower in patients who died. The proportion of patients with leukocytosis, hyperkalemia, metabolic acidosis, pneumonia/ARDS, seizure/encephalopathy, need for ICU support, and dialysis was significantly higher in patients who died. CONCLUSIONS: Snakebite and multiple Hymenoptera stings (bees and wasps) were the leading causes of AKI due to venomous animals. AKI was severe, a high proportion required dialysis, and the mortality was high.