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  ~ Table of Contents - Current issue
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July-August 2020
Volume 30 | Issue 4
Page Nos. 215-294

Online since Thursday, August 20, 2020

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SPECIAL ARTICLES  

NOTTO transplant specific guidelines with reference to COVID-19 p. 215
Vivek Kute, Sandeep Guleria, Jai Prakash, Sunil Shroff, Narayan Prasad, Sanjay K Agarwal, Santosh Varughese, Subhash Gupta, AG K Gokhale, Manisha Sahay, Ashish Sharma, Prem Varma, Anil Bhalla, Harsh Vardhan, Manish Balwani, Shruti Dave, Dhamendra Bhadauria, Manish Rathi, Dhananjay Agarwal, Pankaj Shah, Vasanthi Ramesh, Rajiv Garg
DOI:10.4103/ijn.IJN_299_20  
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KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention and prevention of chronic kidney disease-mineral and bone disorder (CKDMBD): Indian commentary p. 221
Anna T Valson, Manisha Sahay, Narayan Prasad, Sanjay Kumar Agarwal, Santosh Varughese, Sishir Gang
DOI:10.4103/ijn.IJN_1_20  
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SYMPOSIUM Top

Foreward p. 234
Balram Bhargava
DOI:10.4103/ijn.IJN_367_20  
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Preface p. 235
Georgi Abraham, Sanjay Kumar Agarwal
DOI:10.4103/ijn.IJN_366_20  
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Chronic kidney disease of unknown etiology: Case definition for India – A perspective Highly accessed article p. 236
YJ Anupama, Suresh Sankarasubbaiyan, Gangadhar Taduri
DOI:10.4103/ijn.IJN_327_18  
Chronic kidney disease of unknown etiology (CKDu) is a form of chronic kidney disease (CKD) that is prevalent in certain rural populations around the world. It is distinct by its clinicopathologic characteristics and has multifactorial etiology, being mostly linked to several environmental toxins. Although the presentation is similar in various regions across the globe, it also differs in subtle ways from region to region. In India too, there have been reports of the disease in several pockets. There is a need for a comprehensive definition to identify the cases accurately to ease clinical diagnosis and facilitate screening of populations in affected areas. This article presents the diagnostic criteria for CKDu proposed in a consensus meeting at Chennai, India, in May 2017.
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Distribution and determinants of chronic kidney disease of unknown etiology: A brief overview p. 241
P Stalin, Anil J Purty, Georgi Abraham
DOI:10.4103/ijn.IJN_313_18  
Globally, 33187000 DALYs and 956000 deaths are attributed to chronic kidney disease (CKD) every year. Diabetes and hypertension are the two most common causes of CKD. Another category of CKD without any known common causes, chronic kidney disease of unknown etiology (CKDu) is also increasingly reported from different regions of the world such as Central America, Sri Lanka, and India. They are predominately observed in agricultural communities where crops such as sugarcane and coconut are commonly cultivated. Young adults and males are at higher risk of developing CKDu. It mainly affects individuals belonging to lower socioeconomic status. Exposure to silica, arsenic, and fluoride might be associated with increased prevalence of CKDu. The role of heat stress in contributing to CKD through dehydration is unclear but cannot be ruled out. Mycotoxins such as aflatoxins and ochratoxins are also found to be associated with CKDu in some settings. Several studies have reported that CKDu has a significant positive association with pesticides used in agriculture such as HCH, Endosulfan, Alachlor, and Pendimethalin. There is also a possible role of infections by Hantavirus and Leptospirosis in acute febrile phase of CKDu. However, there is no conclusive evidence from studies conducted on CKDu regarding its causes and risk factors. Therefore, large-scale studies with better methodology need to be conducted to study the etiology and pathogenesis of CKDu in various settings.
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A review of chronic kidney disease of unknown etiology in Sri Lanka, 2001–2015 Highly accessed article p. 245
Prabhdeep Kaur, Nalika Gunawardena, Jacob Kumaresan
DOI:10.4103/ijn.IJN_359_18  
An increase in the prevalence of chronic kidney disease of unknown etiology (CKDu) was observed in several countries of the world since the early 2000s. We reviewed the literature to summarize the existing knowledge regarding epidemiology, clinical features, and risk factors for CKDu in Sri Lanka. We reviewed published literature from PubMed and unpublished literature from literature repository of CKDu published by the World Health Organization. We identified 36 articles based on various inclusion/exclusion criteria and reviewed the full text of all selected articles. The prevalence of CKDu was approximately 5% in endemic areas based on the surveillance data. CKDu accounted for 70% of CKD cases in endemic areas. Clustering of cases was observed in select divisions and districts in the dry region of the country. Low body mass index, normal blood pressure, scanty proteinuria, and tubulointerstitial pathology were characteristics of early stages of a disease. Genetic susceptibility, farmer as occupation, heavy metals (cadmium and arsenic), and drinking well water were identified as risk factors. Data were limited on the association with agrochemical use and heat stress/dehydration. Community- and facility-based surveillance needs to be strengthened to document the burden of disease and trends over time.
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Pathology of uddanam endemic nephropathy p. 253
Swarnalata Gowrishankar, Priyanka Koshy, Milly Mathew, N Gopalakrishnan, V Siva Kumar, Georgi Abraham
DOI:10.4103/ijn.IJN_363_18  
In the last decade, pockets of endemic nephropathy have been recognized worldwide, in regions of Central America, Sri Lanka, and India. In India, the nephropathy has been recognized in the Uddanam area of north Andhra Pradesh and has been termed the Uddanam endemic nephropathy (UEN). The disease is distinctive in that besides the geographic distribution, it affects rural populations engaged in farm labor and agriculture, often silent in the initial phase with most patients presenting with advanced renal failure. The renal biopsy findings in all geographic areas including UEN have been one of a chronic tubulointerstitial nephritis with varying degrees of tubular injury, interstitial inflammation, tubular atrophy, and interstitial fibrosis with nonspecific glomerular obsolescence and lack of immune deposits. More recently, the demonstration of dysmorphic lysosomes in renal biopsies has favored a toxic etiology. There are thus many gaps in the understanding of this serious disease prevalent among poorer populations.
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Dietary management in slowing down the progression of CKDu p. 256
Priya Haridas Anupama, Narayan Prasad, Victorine B Nzana, JP Tiwari, Milly Mathew, Georgi Abraham
DOI:10.4103/ijn.IJN_366_18  
Chronic kidney disease of unknown etiology (CKDu) is an emerging entity in the South Asian region. This predominately affects the farming community belonging to the lower socioeconomic status.CKDu being a progressive condition often leads to end-stage renal failurerequiring renal replacement therapy (RRT). Due to the high cost and limited availability of RRT in many areas of geographical locations in India and worldwide, there is an unmet need to slow down the progression of CKDu. The intestinal microbiota is different in patients with CKD, with low levels of beneficial bacteria such as Lactobacillus and Bifidobacteria. Prebiotics and probiotics modify the intestinal microbiota and thereby slow down the progression. Soda bicarbonate therapy is cheap and cost-effective in slowing down the progression of CKDu in a subset of patients. There is also evidence of the beneficial effect of N-acetyl cysteine in early stages of CKD and it should benefit CKDu also. Dietary interventions to prevent dehydration, by providing uncontaminated drinking water, sufficient protein containing diet with adequate calories, and tailored salt intake to prevent hypotension, are necessary compared to other causes of CKD.The objective is to prevent malnutrition, and uremic symptoms. Early diagnosis and prompt intervention may delay the progression of CKDu in the early stages.
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Options of renal replacement therapy in CKDu p. 261
Santosh Varughese, Sanjay K Agarwal, T Ravi Raju, Tripti Khanna
DOI:10.4103/ijn.IJN_396_19  
Patients with advanced Chronic Kidney Disease of Unknown origin (CKDu) need to plan for renal replacement therapy. The patients usually affected are probably best served with living-related renal transplantation. Potential donors from the same area are possibly at risk for developing CKDu and need close monitoring post kidney donation. Peritoneal dialysis (PD) is probably a better option as hemodialysis (HD) centers are located in urban areas only and patients have the convenience of receiving therapy at home. The “PD first” pilot project of Sri Lanka is a unique initiative that trains community physicians to offer PD to patients with advanced CKDu. In Telengana and Andhra Pradesh, the Aarogyasri insurance scheme provides for poor patients to avail of free HD and transplantation in government and private hospitals. Much more needs to be done to care for all those who are affected. A public–private partnership model for providing comprehensive care to patients with advanced CKDu can be undertaken in all areas affected by CKDu that makes renal replacement therapy (RRT) available and accessible, irrespective of financial and social limitations.
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ORIGINAL ARTICLES Top

Gerontolizing nephrology: Spectrum of histopathological findings of kidney biopsy in the elderly p. 264
Pankaj Beniwal, Shailendra K Singh, Vinay Malhotra, Dhananjai Agarwal, Manish Sharma, Parvati Joshi, Shikha Khandelwal, Nisha Gaur, Sanjeev Sharma
DOI:10.4103/ijn.IJN_275_19  
Introduction: The spectrum of renal disorder in the elderly differs from the younger population. There is a paucity of literature regarding kidney biopsy in elderly. This study aims to highlight the clinical profile and histopathological spectrum of the elderly patient undergoing a renal biopsy. Materials and Methods: This retrospective study included all patients (age ≥60 years) undergoing native renal biopsies from January 2012 to December 2017. The clinical profile, laboratory parameters, and renal biopsy findings of these patients were recorded from the case files. Results: Out of 1656 renal biopsies performed during the study period, 230 (13.9%%) performed on the elderly were included. Mean age was 64.02 ± 7.87 years (Range: 60-87 years), and males were predominant (70.4%). The commonest indication for biopsy was nephrotic syndrome (NS) (49.6%) followed by Rapidly progressive renal failure (RPRF) (20.9%) and Acute Kidney Injury (AKI) (15.7%). The most frequent histological diagnosis was membranous nephropathy (15.2%) followed by amyloidosis (13.9%) and Focal Segmental Glomerulosclerosis (FSGS) (13.0%). The commonest cause of NS was MGN (29.8%) followed by FSGS (24.6%) and amyloidosis (22.8%). The commonest cause of nephritic syndrome was Diffuse Proliferative Glomerulonephritis (29.4%) and Membranoproliferative Glomerulonephritis (29.4%). Hypertensive nephrosclerosis (40.0%) and diabetic nephropathy (26.7%)) were the commonest histological diagnosis in the patients who underwent renal biopsy for clinical Chronic kidney disease. Crescentic GN (35.4%) and Myeloma cast nephropathy 14.6%) were the commonest cause of RPRF while Acute Tubular Necrosis (41.7%) was the commonest cause of AKI. None of the patients had major complications. Conclusion: Renal biopsy is safe in the elderly and provides a wealth of information with regards to the diagnosis and prognosis of renal disorder.
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Transforming growth factor-beta 1 and endoglin levels in congenital solitary functioning kidney p. 270
Nuran Cetin, Nadide Melike Sav, Zeynep Kusku Kıraz, Aylin Gencler
DOI:10.4103/ijn.IJN_111_19  
Introduction: Glomerular hyperfiltration leads to hypertension, microalbuminuria, and impaired renal function in children with congenital solitary functioning kidney (cSFK). The purpose of this study was to investigate the associations between serum transforming growth factor β-1 (TGF) and endoglin levels and hypertension, renal function or microalbuminuria in children with cSFK. Materials and Methods: 63 patients and 36 controls were included in the study. Serum endoglin and TGF-β1 level was measured using ELISA commercial kits. Results: Serum TGF-β1 and endoglin levels were higher in patients than those of controls (P = 0.04 and P < 0.001, respectively). The prevalence of hypertension was found to be 45.6%. There was a positive association between endoglin levels and the presence of masked hypertension (odds ratio: 1.121, P = 0.04). TGF-β1 and endoglin levels were positively associated with microalbuminuria (OR: 1.17, P = 0.04; OR: 1.836, P = 0.01). ROC curve analysis showed that serum endoglin and TGF-β1 levels had predictive value for microalbuminuria (cut-off value: 4.86 ng/mL, sensitivity: 94.7%, specificity: 54.5%, area under the curve ± standard error [ AUC ± SE]: 0.888 ± 0.025, P = 0.01 for endoglin; cut-off value 561.24 pg/mL, sensitivity: 89.5%, specificity: 73%, AUC ± SE: 0.995 ± 0.334, P = 0.02 for TGF-β1). There were no significant relationships between glomerular filtration rate and serum TGF-β1 or endoglin levels. Conclusions: Endoglin and TGF-β1 may play an important role in the pathophysiology of microalbuminuria in cSFK. Endoglin may have a role in the development of hypertension in children with cSFK.
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Nephrology postgraduate training in peritoneal dialysis: An online survey p. 277
Sangeetha Lakshmi, B Varalakshmi, N Sai Sameera, A Sunnesh, R Ram, V Siva Kumar
DOI:10.4103/ijn.IJN_184_19  
Introduction: One of the reasons for the peritoneal dialysis (PD) underutilization is related to the training of nephrology postgraduates in PD. This notion is not yet investigated in our country. Methods: We gathered the emails of the heads of the departments of nephrology of all medical colleges and the institutes, which impart DM nephrology post-graduation. We sent the questionnaire framed on the postgraduate training of PD. We received the questionnaire responses anonymously. The broad headings in the questionnaire are information on training resources, training activities, perceived adequacy of the training, and the factors, which limit the utilization of PD. Results: There are 42 medical colleges and institutes (excluding Sri Venkateswara Institute of Medical Sciences) that impart DM nephrology post-graduation in our country. Of these, 30 heads of the departments had responded. More than half of the heads of the department felt that the PD training postgraduates were inadequate. When asked to describe the reason for the perceived inadequacy of PD training, the primary reason noted included was insufficient numbers of PD patients (66.67%). Discussion: The conclusion may be drawn from our study that the postgraduate training in PD in our country is gratifying. Our hypothesis that a lacuna in postgraduate training in PD may be one of the reasons for the underutilization of PD seems ungrounded.
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CASE REPORTS Top

Novel homozygous FAN1 mutation in a familial case of karyomegalic interstitial nephritis p. 283
Priyanka J Koshy, Digumarthi V. S. Sudhakar, Sneha H Anupama, Milly Mathew, Rajeevalochana Parthasarthy, Kumarasamy Thangaraj, Muhammad Magdi Yaqoob, Georgi Abraham
DOI:10.4103/ijn.IJN_278_19  
Karyomegalic interstitial nephritis (KIN) is a rare genetic kidney disease associated with a mutation in FAN1 gene and is often underdiagnosed. The histomorphology demonstrates chronic interstitial nephritis with tubular epithelial cells showing bizarre enlarged nuclei. We present a case report of a 47-year-old multiparous South-Indian woman presenting with bilateral pitting pedal oedema and mild hypertension. At the time of presentation, her serum creatinine was 1.52 mg/dL and urine analysis showed mild proteinuria. Kidney biopsy showed features of tubular injury with bizarre enlarged nuclei and focal mild chronic tubulointerstitial nephritis. Immunohistochemistry was negative for cytomegalovirus (CMV) Ag and SV40 Ag. Real-time polymerase chain reaction (PCR) done for CMV and BK virus genomes was negative. Relevant family history was that her older brother was also diagnosed with kidney failure and is on renal replacement therapy. Genetic analysis for FAN1 gene of the proband and her sibling showed two rare mutations of the FAN1 gene in the exon 4, of which, one is non-synonymous mutation and the other is a stop-gain mutation in the proband. This case illustrates a rare presentation of karyomegalic interstitial nephritis in siblings with previous unknown FAN1 gene mutations.
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Novel variation in CFB adult onset atypical hemolytic uremic syndrome: A case report and review p. 286
Malsawmkima Chhakchhuak, Jony Agarwal
DOI:10.4103/ijn.IJN_265_19  
We report a case of 47-year-old male with atypical hemolytic uremic syndrome (aHUS). He had low C3 levels and whole exome sequencing revealed heterozygous missense novel variation in exon 8 of the gene encoding complement factor B (CFB), leading to substitution of leucine for proline at codon 369 (c.1106C>T; p.Pro369Leu). Following plasma exchanges and hemodialysis, the patient achieved hematological remission and became dialysis independent.
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Crystalline nephropathy due to APRT deficiency: A preventable cause of renal and renal allograft failure p. 290
Prashant Rajput, Zaheer A Virani, Bharat V Shah
DOI:10.4103/ijn.IJN_106_19  
Adenine phosphororibosyl transferase (APRT) deficiency, a rare inborn error of metabolism is inherited as an autosomal recessive trait. It presents with 2,8-dihydroxyadenine (2,8-DHA) crystal nephropathy and recurrent nephrolithiasis and often progresses to end stage renal disease (ESRD). After transplant, it can recur in the allograft. If APRT deficiency is recognized early, renal failure can be prevented, arrested or reversed in native kidney and in allograft by treatment with allopurinol, which inhibits xanthine oxidase and reduces 2,8-DHA formation. We report two cases of APRT deficiency from our center. DNA sequencing of APRT gene performed in one of the cases revealed a pathogenic variant in Exon1 of APRT gene (c.3G>C; p.Met1). This variant affects the translation initiation codon and results in a start loss. The variant has previously been reported in two cases with APRT deficiency.
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LETTERS TO EDITOR Top

Study of FGF 23 levels in patients with acute kidney injury and its outcome p. 293
Krishan Lal Gupta, Tirthankar Mohanty, Vivek Sood, Raja Ramachandran
DOI:10.4103/ijn.IJN_218_19  
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Indian Journal of Nephrology
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Online since 20th Sept '07