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   Table of Contents - Current issue
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January-March 2020
Volume 14 | Issue 1
Page Nos. 1-84

Online since Tuesday, March 31, 2020

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EDITORIAL  

Corona, COVID and kidney transplantation Highly accessed article p. 1
Manisha Sahay, Vivek Kute, Narayan Prasad
DOI:10.4103/ijot.ijot_21_20  
Severe acute respiratory syndrome corona virus 2 (SARS CoV2) is responsible for corona virus disease (COVID-19). Many organizations have given guidelines for the prevention of COVID-19. Other societies have given updates regarding living and deceased donor transplantation during the pandemic. This article reviews the literature available on corona virus and its impact on living and deceased donor transplantation.
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COMMENTARY Top

Thrombotic microangiopathy and rejection in blood group incompatible renal transplantation Highly accessed article p. 5
Praveen Kumar Etta
DOI:10.4103/ijot.ijot_68_19  
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REVIEW ARTICLES Top

Therapeutic drug monitoring of tacrolimus in kidney transplantation p. 8
Shyam Bihari Bansal
DOI:10.4103/ijot.ijot_4_20  
Calcineurin inhibitors (CNI) are the backbone of present-day immunosuppressive regimen in kidney transplant recipients. Tacrolimus (TAC) has gradually replaced cyclosporine as CNI of choice due to its better potency and side effect profile. One of the key challenges in using TAC is therapeutic drug monitoring (TDM) of TAC, as it is a drug of narrow therapeutic index. Various methods of TDM are available; there are older immunoassay (IA)-based methods and recent liquid chromatogram (LC) based. The problems with older IAs like microparticle enzyme IA (Abbott Diagnostics, Chicago, IL, USA), and enzyme multiplied IA (EMIT, Dade Behring, Glasgow, DE, USA) are; they are not so accurate, there is interference with other substances, they measure inactive metabolite, and their limit of detection is not wide. The LC-based methods such as liquid chromatogram mass spectroscopy or LC-tandem mass spectroscopy overcome these issues; however, they are costly, labor intensive, and require good technical support. Newer IAs, such as chemiluminescent microparticle IA (Abbott Diagnostics) and Quantitative Microsphere System (QMS™, Thermo-Fisher), have functional sensitivity <1 ng/ml, and overcome the disadvantages of older IAs. These newer IA are reported to offer adequate accuracy and precision, and at the same time, they are easy to perform. There is genetic variation in expression of cytochrome p-450 (CYP3A4) and CYP3A5 enzymes, which metabolizes TAC, resulting in different levels with same doses. Patients who are expressers (CYP3A5 1*/1* OR CYP3A5 1*/3*) require higher doses to maintain the same levels compared to nonexpressers (CYP3A5 3*/3*).
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Malnutrition in kidney transplantation: Our experience and review of literature p. 15
Sneha Haridas Anupama, Georgi Abraham, Rajeevalochana Parthasarathy, Priya Haridas Anupama, Milly Mathew
DOI:10.4103/ijot.ijot_40_19  
Malnutrition is a well-known determining factor in the clinical outcome of a patient posttransplant. Malnutrition encompasses the entire spectrum ranging from excess to deficiencies of calorie, protein, and macronutrient and micronutrient intake. Pre- and posttransplant nutritional status of the patient is directly proportional to the graft survival. The misperception that transplantation would appease dietary restrictions in conjunction with inadequate physical activity adds to the burden of posttransplant complications. Commonly encountered complications posttransplant include weight gain, hypertension, cardiovascular disease, and new-onset diabetes mellitus. While various studies have shown the effect of pretransplant serum phosphorus albumin, alkaline phosphatase, and body mass index on posttransplant functional graft survival, posttransplant malnutrition leading to an array of metabolic disorders can equally affect the same. The lack of standardized guidelines for the assessment and prevention of malnutrition specifically targeted at reducing posttransplant morbidity and mortality is the need of the hour. The focus must be on the implementation of a comprehensive patient-specific dietary and lifestyle plan made in collaboration by the patients treating physician, a skilled nutritionist, and family, taking into consideration adequate micronutrient and macronutrient requirements and patients' socioeconomic background.
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ORIGINAL ARTICLES Top

Seth-donation of organs and tissues (S-DOT) score: A scoring system for the assessment of hospitals for best practices in organ donation after brain death p. 19
Avnish Kumar Seth, Twinkle Singh
DOI:10.4103/ijot.ijot_49_19  
Background: A need was felt to have a simple scoring system for the objective assessment of hospitals for preparedness for donation after brain death (DBD). Materials and Methods: Eighteen tertiary care transplanting hospitals in India were scored on 20 parameters (Seth-Donation of Organs and Tissues [S-DOT] score). An independent observer scored each parameter as 2, 1, or 0 with a maximum score of 40. The loopholes in organ donation (OD) were addressed by monthly interactions and hospitals re-assessed at 6 months by the same observer. Statistical analysis was performed with the Wilcoxon signed-ranks test. Results: The median S-DOT score at baseline was 13.5 (range 3–33). On correlating baseline score with donations over preceding 4 years, 1 hospital with score >30 (good) had 17 donations, 8 hospitals with a score 15–29 (satisfactory) had 19 donations, whereas none of the 9 hospitals with score <15 (unsatisfactory) had a donation. After 6 months, S-DOT score improved for all hospitals to a median of 23.5 (range 4–37) with a median increase of 6.7 (range 1–22), P < 0.001. Four hospitals with a score >30 had 6 donations, 9 hospitals with score 15–29 had 7 donations whereas none of the 5 hospitals with score <15 had any donation. Conclusion: S-DOT score may be a useful tool for the objective assessment and improvement of hospitals on best practices in DBD. A score of >30 was frequently associated with OD, while a score <15 could consistently identify hospitals that did not have any donation.
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Short-term mineral metabolism adaptation in living kidney donors: A prospective study p. 25
Mital Dipakkumar Parikh, Sishir Gang
DOI:10.4103/ijot.ijot_61_19  
Background: Living kidney donors (LKDs) show an abrupt decline in glomerular filtration rate (GFR) however, mineral metabolism adaptations in early chronic kidney disease (CKD) are still debated and not well studied in LKDs. We prospectively studied short term mineral metabolism adaptation of LKDs. Material and Methods: From January 2017 to April 2017, we included 36 adult LKDs. Their mineral parameters and renal function were repeatedly measured at days 0 and day 30 after kidney donation. Results: In the 1st month after nephrectomy, urinary phosphate reabsorption increased nonsignificantly in spite of significant increase in circulating fibroblast growth factor 23 (FGF23). LKDs have lower estimated GFR (eGFR) and unchanged 1,25-dihydroxyvitamin D (25(OH) 2D). Conclusion: Short-term mineral metabolism adaptations to decreased eGFR in donors include unchanged 25(OH) 2D unchanged fractional excretion of phosphate and increase in phosphate reabsorption with significant increase in FGF23. These adaptations differ from those described in CKD patients.
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Current knowledge status and attitude on heart transplantation among undergraduate medical students of a tertiary care medical institute in India p. 30
Anshuman Darbari, Manisha Naithani, Suresh Kumar Sharma, Anish Gupta, Ajay Kumar, Deepak Kumar Satsangi
DOI:10.4103/ijot.ijot_47_19  
Context: Organ transplantation can save thousands of lives as it is one of the greatest advancements of modern medical science but the process of organ donation and transplantation is very complex and multi-factorial, interplaying with- medical, legal, ethical, organizational and above all social factors. The future doctors can take up the role of promoting organ donation activity, especially the heart. Settings and Design: This cross-sectional questionnaire based survey study was conducted amongst the undergraduate medical students of our Institute, to ascertain their knowledge and ethical perception regarding orthotropic heart transplantation. Methods and Material: Students were approached in lecture halls and were asked to fill the questionnaire after explaining them the importance of this study in brief. Written consent for participation was taken from all of them. A total of 197 undergraduate students gave consent and filled the questionnaire. Statistical Analysis Used: All the quantitative variables were analyzed using mean and standard deviation and all the qualitative variables were described as numbers and percentages. Results: Nearly all the students knew the term organ donation and heart transplantation but in-depth knowledge of medical students on this topic was not good enough. Most participants (75%) considered “Internet“ as their major source of information, while only 01% regarded academic books as their source of information. This strongly highlights the point that the undergraduate medical books with curriculum is largely lacking in basic aspects of organ donation and heart transplantation. Very few medical students (4.5%) knew about the Non-Governmental Organization (NGOs) working for transplant activity and also majority (82.2%) are unaware of legal aspects related to organ donation. Conclusions: Currently heart transplantation is a totally neglected topic in undergraduate medical curriculum. Inclusion of this complex but interesting topic by a short lecture or interactive seminar for undergraduate medical students may be the most cost-effective and durable innovation for the future.
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Delayed graft function in living donor kidney transplantation: A single-center experience p. 38
Rakesh Durai, Gopalakrishnan Natarajan, Dinesh Kumar Thanigachalam, Sakthirajan Ramanathan, Dhanapriya Jeyachandran, Deepak Kumar
DOI:10.4103/ijot.ijot_23_19  
Aim: The aim was to study the incidence of delayed graft function (DGF) in living donor kidney transplantation (LDKT), its risk factors, and its impact on graft and patient survivals. Materials and Methods: We retrospectively analyzed the medical records of 543 patients over 12 years of age who had received kidney transplant from a living donor between 2007 and 2018. The demographic characteristics of the patients, acute rejection rates, graft function at 1 year, graft survival, and patient survival were compared between patients with and without DGF. Results: The incidence of DGF was 10.1% in our study. Cold ischemia time (CIT) (76.61 ± 33.66 vs. 53.02 ± 17.55 min; P < 0.01) and the use of tacrolimus (6.3% vs. 4.2%; P < 0.01) were associated with greater incidence of DGF. Patients with DGF had a longer duration of hospital stay (23.03 ± 11.37 vs. 13.98 ± 5.81 days; P < 0.01). There were no statistically significant differences in acute rejection rates, death-censored graft survival, and patient survival in the two cohorts. Conclusions: Our study reiterates that CIT is an important predictive factor for DGF. This is pertinent because CIT is a modifiable risk factor. However, DGF did not have a significant impact on patient and graft survivals in LDKT recipients.
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In vitro lymphocyte culture-based allo-specific cytokine response profiles predictive of acute rejection in kidney allografts p. 42
Sobhana Mahakur, Mukut Minz, Ranjana Walker Minz, Ritambhra Nada, Ashish Sharma, Mehak Bhasin, Biman Saikia
DOI:10.4103/ijot.ijot_57_19  
Background: In vitro allo-specific cytokine response to prospective allograft antigens might provide a means to identify patients at risk to adverse clinical endpoints/graft failure and predict allograft survival after transplantation. Methods: Cytokine profiles of recipient's peripheral blood mononuclear cells cocultured with allograft antigen-pulsed recipient macrophages were studied in 49 renal transplant recipients, 19 of which has acute rejection-12 with acute cellular rejection (ACR) and 37 non-ACR allografts. Cytometric bead array was used to analyze 18 cytokines/chemokines in the culture supernatants of graft antigen-pulsed and un-pulsed cultures. The mean increment in cytokine expression in stimulated versus unstimulated cultures was calculated. Results: Interleukin 6 (IL-6) (2336.42 ± 213.4 vs. 1244.06 ± 224 fg/ml; P = 0.0070), IL-1α (28.3 ± 7.451 vs. 16.78 ± 5.513 fg/ml; P = 0.0417), IL-17A (201 ± 96.73 vs. 28.91 ± 18.45 fg/ml; P = 0.0262), and MIP-1α/CCL3 (2682.25 ± 1013 vs. 1748.99 ± 780.4 pg/ml; P = 0.0383) were found to be high in rejection compared to stable allografts. Similarly, IL-6, IP-10/CXCL10, MIP-1α, and MCP-1 were increased in ACR, whereas granzyme B (11.36 ± 7.974 vs. 28.71 ± 9.393 pg/ml; P = 0.0011) and RANTES/CCL5 were higher in the non-ACR group. Conclusion: Distinct allo-specific in vitro cytokine profiles correlated with the occurrence of posttransplantation rejection episodes in the cohort, which indicated the feasibility of this in vitro model to predict transplant outcomes.
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Quality of life among liver transplantation recipients before and after surgery: A single-center longitudinal study p. 48
Alireza Shamsaeefar, Saman Nikeghbalian, Kourosh Kazemi, Sivash Gholami, Mehrab Sayadi, Fatemeh Azadian, Nasrin Motazedian, Seyed Ali Malekhosseini
DOI:10.4103/ijot.ijot_42_19  
Background: Liver transplantation has improved patients' survival rates and quality of life (QoL). This study investigated the effect of liver transplantation and model for end-stage liver disease (MELD) score on patients' QoL at Shiraz Organ Transplantation Center. Materials and Methods: This perspective longitudinal study was conducted among 40 liver transplant candidates at Shiraz Organ Transplant Center. Inclusion criteria were patients who were 12 years or older, able to answer the questions and willingness to participate. If they had received multi-organ transplant and had mental or physical disabilities, we excluded them from the study. They were interviewed by the same researcher in the transplant clinic before transplantation, 1 and 6 months after transplantation. The participants completed the data collection form and Short Form-36 questionnaire via face-to-face interview. The data collecting form consist of demographic and medical information. Medical information was collected from Shiraz Organ Transplant Center. Results: Mean age of participants was 41.18 ± 14. By comparing QoL dimensions, a significant difference was found between before and after transplantation (P < 0.001), except in General Health dimension (P = 0.711). There was no statistically significant relationship between MELD score and QoL after liver transplantation (P > 0. 05). Conclusion: Liver transplantation improves patients' quality life with end-stage liver disease. MELD scores do not depict QoL after liver transplantation.
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Usefulness of real-time sonoelastography for assessment of renal allograft fibrosis p. 53
Ram Dayal Sahu, Dharmendra Kumar Jangid, Devendra Singh Dhaker, Vinay Rathore, Shubham Agrawal, Sher Singh Yadav, Dhananjai Agrawal, Parvati Joshi
DOI:10.4103/ijot.ijot_53_19  
Background: Currently, allograft renal biopsy is the only reliable tool available to detect fibrosis in the transplanted kidney. However, it is an invasive procedure and is associated with complications. Therefore, a noninvasive tool to detect renal allograft fibrosis is needed. Aims: The aim of the study was to evaluate the usefulness of real-time sonoelastography (RTS) in the diagnosis of renal allograft fibrosis. Subjects and Methods: We studied 15 renal allograft recipients who had chronic allograft nephropathy. RTS was performed by an experienced radiologist to semi-quantitatively determine cortical and medullary stain ratio. These parameters were compared with the degree of fibrosis as assessed by allograft renal biopsy. For comparison, patients were divided into two groups based on the degree of fibrosis: those with mild fibrosis (interstitial fibrosis and tubular atrophy [IFTA] <25%) and those with moderate-to-severe fibrosis (IFTA >25%). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of cortical strain ratio to discriminate between patients with mild fibrosis versus patients with moderate-to-severe fibrosis. Results: The mean cortical strain ratio was significantly higher in those who had mild fibrosis as compared to those who had moderate-to-severe fibrosis (2.46 ± 0.55 vs. 1.78 ± 0.15, P = 0.01), while the medullary strain ratio was comparable between the two groups. The diagnostic accuracy of cortical strain ratio, as evaluated by area under the curve of ROC analysis, was 0.96. Conclusion: RTS can differentiate between mild fibrosis and moderate-to-severe fibrosis with high accuracy.
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What are the factors affecting survival after autologous stem cell transplantation in patients with multiple myeloma? p. 57
Serife Solmaz, Celal Acar, Ahmet Seyhanlı, Omur Gokmen Sevindik, Ozden Piskin, Mehmet Ali Ozcan, Fatih Demirkan, Bülent Undar, Inci Alacacioglu, Guner Hayri Ozsan
DOI:10.4103/ijot.ijot_15_19  
Introduction: High-dose chemotherapy (HDC) and autologous stem cell transplantation(ASCT) still remains in the treatment of myeloma patients even during the period of new agents. Materials and Methods: We analysed the prognostic affect of pretransplant characteristics and transplant modalities on response, in 150 autologous transplant of 144 multiple myeloma (MM) patients who were transplanted in our centre between 2008 to 2017. We evaluated the affect of age, type of MM, previous treatment regimens, status pre and postfrom transplantation, time of ASCT, neutrophil and platelet engraftmant days, dose of reinfused CD34+ cells, plasma cell infiltration, international staging system(ISS) and Durie -Salmon stage at diagnosis. We examined the affect of these status on overall survival(OS) and eventfree survival(EFS). Results: The median OS and EFS after transplanation were 41 and 28 months, respectively. Median OS after the diagnosis was 57 months. Transplant-related mortality was 3,3%. We found that the lower β2- microglobulin levels,lower ISS stage,lower plasma cell infiltration, achievement good responds at the +100th day of post transplant were statistically significant independent predictor factors for longer EFS and OS. When the patients were given chemotherapy regimen with bortezomib before transplantation, these patients were seen to be a better response rate. There was showed a relationship between the using of bortezomib before transplantation with EFS(P = 0.017), but there was no relationship with OS. Conclusions: Our analysis confirms HDCT-ASCT as an effective and safe therapeutic strategy in multiple myeloma patients. This results were independent of age, first line treatment regimens and renal insufficiency. Patients with a high ISS stage were found to have shorter survival(P = 0.002). However, the EFS and OS were longer of the patients whose have good response at the 100th day of transplantation(P = 0,002, P = 0,02).
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Survival after liver transplant in recipients older than 70 years: A systematic review and meta-analysis p. 63
Karn Wijarnpreecha, Panadeekarn Panjawatanan, Omar Y Mousa, Wisit Cheungpasitporn, Frank J Lukens, Justin H Nguyen, Surakit Pungpapong, Denise M Harnois, Patompong Ungprasert
DOI:10.4103/ijot.ijot_59_19  
Background/Objectives: More elderly patients with end-stage liver disease are receiving liver transplantation. However, data on outcome of recipients older than 70 years are still limited. The current systematic review and meta-analysis was conducted with the aim to better describe the survival outcome of liver transplant in recipients older than 70 years compared to younger recipients. Methods: A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through March 2019 to identify all cohort studies that compared the long-term survival outcome between patients who underwent liver transplantation at age of >70 years versus younger recipients. Effect estimates from each study were extracted and combined together using the random-effects, generic inverse variance method of DerSimonian and Laird. Results: A total of 5 studies with 19,757 participants fulfilled the eligibility criteria and were included in the meta-analysis. The mortality rate was significantly increased among recipients who were 70 years or older compared to younger recipients with the pooled hazard ratio of 1.72 (95% confidence interval: 1.43–2.06; I2: 16%). Conclusions: The current study demonstrated a significantly increased risk of mortality postliver transplantation among recipients older than 70 years. This could be useful information to be considered along with other factors to establish graft allocation policy.
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CASE REPORTS Top

Polymicrobial meningitis in a renal transplant recipient – “cryptococcus neoformans and acinetobacter baumannii coinfection with elizabethkingia meningoseptica superinfection“ p. 68
Vivek Sood, Shefali Gupta, Raja Ramachandran, Krishan Lal Gupta
DOI:10.4103/ijot.ijot_52_19  
Although rare, polymicrobial meningitis has been infrequently reported in renal transplant recipients (RTRs). In this context, we describe a RTR on triple immunosuppression therapy, with stable graft function, who had presented with fever and altered sensorium of 2 days' duration. Evaluation revealed polymicrobial meningitis, which was initially attributed to concurrent infection by Cryptococcus neoformans and Acinetobacter baumannii and was later superinfected with Elizabethkingia meningoseptica. The overall prognosis in polymicrobial meningitis remains dismal, re-emphasizing the importance of early suspicion and prompt microbiological diagnosis for targeted antimicrobial therapy.
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Early recurrence of C3 glomerulopathy postrenal transplant manifesting as rapid progressive glomerulonephritis p. 71
Sameer Bhuwania, Sanjiv Saxena, Ravi Bansal, Rajesh Goel
DOI:10.4103/ijot.ijot_44_19  
Renal transplant is the definitive treatment of choice for patients with end-stage renal failure and owing to the cost and problems involved with the surgery, long-term survival of the graft is a very important aspect of care. Primary glomerular disease recurrence is a dreaded complication of any kidney graft since it is impossible to prevent it with no guidelines or recommendations. C3 glomerulopathy is a condition which has very high recurrence rate after renal transplant, but rapid recurrence in a case who had a benign course of illness pretransplant is unique to this patient and needs to be discussed.
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Successful treatment of transplant renal artery stenosis with bare-metal stent in a patient with simultaneous pancreas and kidney transplantation p. 75
SP Shivakumar, Deepesh B Kenwar, Ashish Sharma, Rajesh Vijayvergiya
DOI:10.4103/ijot.ijot_35_19  
Transplant renal artery stenosis (TRAS) is a well-recognized vascular complication after renal transplantation. It occurs most frequently in the first 6 months after renal transplantation and is a reversible cause of hypertension, volume overload, and graft dysfunction or graft loss. Early diagnosis and endovascular intervention (EVI) result in good outcome. The present report describes a challenging case of TRAS with diagnostic dilemma in a Type I diabetic patient with end-stage renal disease who had undergone a simultaneous pancreas and kidney transplantation. The patient had multiple risk factors for TRAS including atherosclerosis, interruption in immunosuppression due to subacute intestinal obstruction, antibody mediated rejection (ABMR) and tortuosity of the implanted artery. He presented with fluid retention and graft dysfunction without significant hypertension. He was initially diagnosed as ongoing ABMR for which he received antirejection therapy without any significant improvement. He was finally diagnosed as TRAS and successfully salvaged with EVI.
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Obstructive hydrocephalus in a renal transplant recipient: An avertable diagnostic delay in unraveling cryptococcal meningitis! p. 79
Vivek Sood, Raja Ramachandran, Shefali Gupta, Neeraj Inamdar, Arun Prabhahar, Krishan Lal Gupta
DOI:10.4103/ijot.ijot_54_19  
Cryptococcal infection constitutes 2.8% of opportunistic infections in solid-organ transplant recipients. The most common organ affected in renal transplant recipients (RTRs) is central nervous system and usually presents with chronic meningoencephalitis. Rapid neurological deterioration in RTR with chronic meningitis despite antimicrobial therapy should alert towards the possibility of either alternative/polymicrobial etiology or complications including hydrocephalus. In this context, we report a RTR with chronic meningitis initiated on empirical antitubercular therapy in the absence of conclusive microbiological diagnosis despite serial cerebrospinal fluid analysis and later admitted with complication in form of obstructive hydrocephalus requiring external ventricular drainage which proved to be therapeutic (decreasing raised intracranial hypertension) as well as diagnostic (yielding Cryptococcus), thereby confirming alternative etiology of chronic meningitis.
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Small caliber aortoiliac arteries in a patient undergoing renal transplantation for iga nephropathy p. 82
RB Nerli, Vishal Kadeli, Aarushi Mishra, C Shridhar Ghagane, Neeraj S Dixit, Murigendra B Hiremath
DOI:10.4103/ijot.ijot_16_19  
IgA nephropathy (IgAN) is a common form of primary glomerulonephritis. Most cases of IgAN are discovered incidentally by abnormal urinalysis (hematuria or proteinuria) and diagnosed by renal biopsy. Nearly 30%–50% of patients with IgAN progress to end-stage renal disease (ESRD) at a follow-up of 25 years. We report a case of small caliber iliac vessels in a patient undergoing renal transplant for ESRD secondary to IgAN.
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