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   Table of Contents - Current issue
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April-June 2019
Volume 13 | Issue 2
Page Nos. 69-150

Online since Friday, June 28, 2019

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REVIEW ARTICLES  

Renal allograft dysfunction: An update on immunological graft injury Highly accessed article p. 69
Praveen Kumar Etta, MV Rao
DOI:10.4103/ijot.ijot_84_18  
Renal transplantation is the treatment of choice in most patients with end-stage renal disease, especially with improvement in surgical techniques and immunosuppressive regimens; however, the long-term graft survival remains to be improved. Immunological graft injury leading to rejection plays a major role in long-term graft loss. With pretransplant immunological evaluation using various crossmatch tests, identification of donor-specific antibodies, a better understanding of renal allograft pathology and its standardization with the Banff classification having regular updates led to prevention, early and accurate diagnosis of rejection and its histological differentiation. Some newer biomarkers are in pipeline may enable early and accurate identification of graft pathology noninvasively.
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Is preimplantation renal biopsy essential prior to deceased donor renal transplant? p. 78
M Edwin Fernando, Sujit Surendran, Ishwarya Annamalai
DOI:10.4103/ijot.ijot_75_18  
The striking discrepancy in the number of end-stage renal disease patients added to the transplant wait list and the shortage of standard criteria donors has stimulated the development of strategies aimed to expand acceptance criteria from marginal deceased donors. Renal biopsy done before transplant will be useful to predict short- and long-term outcomes of kidney transplantation. It also serves as a reference in interpretation of subsequent biopsies. It also helps in deciding whether it should be discarded. However, systemic reviews concluded that there was no consistent association between donor biopsy findings and posttransplant outcomes. A well-designed randomized control trial could ascertain the extent of procurement biopsy leading to discards, whether outcomes are indeed better when preimplantation biopsies are used to justify declining kidneys for transplantation.
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ORIGINAL ARTICLES Top

A study of sociodemographic profile and level of awareness of the decision makers for organ donation of deceased organ donors in a Tertiary Care Hospital p. 82
Navdeep Bansal, Vipin Koushal, Aditi Mehra
DOI:10.4103/ijot.ijot_51_18  
Aim: Organ transplants have developed into a successful therapy to treat end-stage organ disease. Family members play a prominent role in decisions related to organ donation of brain-dead patients. Having different imaginations about brain death among the people may be highly influenced by culture, experience, and other sociodemographic variables. Thus, the study was undertaken to analyze the sociodemographic profile of the decision makers for organ donation in case of potential deceased donors and to determine the level of awareness and its relation with the sociodemographic variables. Methods: The study was conducted at a tertiary care hospital of North India from January 2016 to August 2017. The current research is a qualitative study with exploratory approach. Data were collected through interviews with 59 family members who gave consent to organ donation of their family members. A purposive sampling method was used. Results: The results showed that most (76.3%) of the decision makers were totally unaware of the concept of organ donation before they were counseled for the same. The results showed that awareness of organ donation was dependent on gender, education, and monthly income. Most of the decision makers had only primary education. Although they were initially not aware about the concept, their decision-making was not influenced by the level of education. Majority (90%) of the females were unaware about the organ donation, but eventually consented for the cause. Conclusion: The scope of mass education and awareness can be expanded to further strengthen the program and improve the outreach.
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Contemporary management of urological complications in renal transplant: Analysis from a single-center with review of the literature p. 86
Pritesh Jain, Dilip Kumar Pal
DOI:10.4103/ijot.ijot_40_18  
Context: Urological complications are inevitable in renal transplantation; however, their occurrence and brunt on graft survival can be downsized. The aim of our study was to analyze and review the literature on various urological complications and their management in renal transplant patients. Materials and Methods: We reviewed all cases of urological complications in renal transplantation managed at our institution from January 2010 to March 2017. Results: Urological complications arose in 29 renal transplant patients amidst the study period with median identification time of 24 days (range 0–1500 days). Ten (34.5%) patients developed complications pertaining to ureteric handling and reimplantation followed by significant lymphocele in 9 (31%) patients. Four (13.8%) cases succumbed to vascular anastomosis-related complications. Out of 29 patients, 45% of these complications manifested within a month posttransplant. Complications were tackled individually. Sixteen (55%) cases were treated with either endoscopic or minimally invasive methods, whereas 13 (45%) cases required open surgery. Two grafts were lost as a consequence of vascular complications and a fatality which was directly or indirectly linked with urological complication. Remaining all treated patients improved on follow-up. Conclusion: Comprehensive preoperative recipient evaluation, meticulous organ procurement, and integrated multidisciplinary teamwork are helpful in achieving optimal outcome of transplant. Endourological and minimally invasive procedures are emerging as main modality in the management of these complications; however, many cases still requires contemporary surgical management.
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Cirrhotic cardiomyopathy- Survival at 3 months after liver transplantation p. 91
Ravikumar Bokarvadia, Mayank Jain, Joy Varghese, Jayanthi Venkataraman
DOI:10.4103/ijot.ijot_60_18  
Background: Cirrhotic cardiomyopathy (CCM) occurs in 39.4%–48.3% of patients with chronic liver disease with or without decompensation. A significant number of patients are likely to be listed for liver transplantation (LT). The early outcome of LT in these patients is not known. Aims and Objectives: The aim is to study the prognostic implication of CCM on survival at 3 months post-LT. Materials and Methods: This prospective study was conducted from July 2016 to July 2017. Patients, who were diagnosed as cirrhosis of the liver based on clinical, biochemical, imaging, and endoscopic findings, were included in the study. After informed consent, details of demography, comorbidity, and cirrhosis-related complication were noted. Cardiac evaluation included electrocardiography, two-dimensional echocardiography, dobutamine stress test, and coronary angiography whenever indicated. CCM was diagnosed based on the standard criteria. Patients who underwent LT were followed up in the posttransplant period up to 3 months. Statistics: Mann–Whitney U-test, Chi-square test, and Kaplan–Meier survival plot were used for statistical analysis. P < 0.05 was considered statistically significant. Results: Five hundred and eighty-six adult patients with cirrhosis of the liver underwent cardiac evaluation. One hundred and ninety-eight (33.8%) patients were diagnosed with CCM. Forty-one patients underwent LT. Following LT, there was an improvement in diastolic dysfunction in a third of patients (12 patients; 29.3%) but with no survival benefit at 3 months (P = 0.23). Higher baseline model for end-stage liver disease and left ventricular diastolic dysfunction were more common among nonsurvivors. Conclusion: CCM does not influence the short-term survival in patients undergoing LT.
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Immunological barriers in ABO-incompatible kidney transplantation: How to overcome p. 96
Sonia Mehrotra, Raj Kumar Sharma
DOI:10.4103/ijot.ijot_76_18  
Background: Various desensitization strategies are used to overcome immunologic barriers such as anti-human leukocyte antigen-donor-specific antibody (HLA-DSA) and anti-ABO blood group incompatibility. Materials and Methods: Three index cases of ABO-incompatible (ABO-i) kidney transplantation from living-related donors are discussed. Each recipient was evaluated by complement-dependent cytotoxicity crossmatch, flow cytometric crossmatch, lysate-based crossmatch, and single-antigen bead Luminex assay and anti-A, B isoagglutinin titer. The desensitization protocol included 500 mg of rituximab, followed by 2–10 sessions of plasmapheresis with basiliximab/antithymocyte globulin induction. Results: Case 1: A patient received the third transplant as ABO-i transplant, with no anti-HLA-DSA. Anti-ABO antibody titers were immunoglobulin M (IgM)/IgG 1:128/1:256. He had successful desensitization to anti-AB titer of <1:2 (IgM/IgG) with excellent outcome. Case 2: At the time of transplant, a patient had no anti-HLA-DSA. ABO titers were reduced to <1:8 (IgM/IgG) from baseline of IgM/IgG 1:128/1:1024 after desensitization. Posttransplant patient had severe acute graft dysfunction within 1 week, with rebound of anti-B titers to (IgM/IgG) 1:128/1:1024. Graft biopsy showed cortical necrosis resulting in graft loss. Case 3: His first ABO-compatible transplant was lost because of de novo anti-HLA-DSA, which developed within 1 week after transplant. The patient underwent the second ABO-i transplant. He also had anti-HLA-DSA against the second donor. Despite desensitization and anti-ABO titers coming down to <1:8, the patient developed severe acute graft dysfunction within 2 weeks, with rebound of anti-HLA-DSA antibody (titers increased >11000) resulting in graft loss. Conclusions: Careful evaluation of immunological barriers before ABO-i transplantation should be done, especially when both anti-HLA and ABO sensitization are present.
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Basiliximab induction in living donor kidney transplant with tacrolimus-based triple immunosuppression p. 104
Shyam Bihari Bansal, Deepak Pathania, Sidharth Kumar Sethi, Pranaw Kumar Jha, Ashish Nandwani, Manish Jain, Amit Mahapatra, Vijay Kher
DOI:10.4103/ijot.ijot_81_18  
Introduction: Interleukin-2 receptor antagonists are recommended to reduce the risk of acute rejection (AR) in kidney transplant. This prospective study was undertaken to compare the incidence of AR with basiliximab induction as compared to no induction in first kidney recipients of living donors with tacrolimus (TAC)- and mycophenolate mofetil-based triple immunosuppression at 6 months. Methods: Two hundred and sixty patients were included in the study, 202 in the basiliximab group and 58 in the no induction group. Patients in the basiliximab group received two doses of 20 mg each on day 0 and day 4. The primary outcome was biopsy-proven AR at 6 months, and the secondary outcomes were incidence of infections and other adverse events along with graft and patient survival at the end of follow-up. All patients were followed up for a period of minimum 6 months. Results: There was no difference in baseline characteristics between the groups except higher human leukocyte antigen mismatch in the basiliximab group (3.80 ± 1.50 vs. 2.81 ± 1.53, P = 0.002). Forty-two (20.8%) patients in the basiliximab group developed AR at 6 months as compared to 10 (17.2%) in the no induction group (P = 0.55). There was no difference in adverse events between the groups. At a median follow-up of 1 year, graft survival (97% vs. 98.3%, P = 0.60) and patient survival (99% vs. 98.2%, P = 0.87) were also similar between the basiliximab and no induction groups, respectively. Conclusions: This study suggests that there is no advantage of using basiliximab induction in reducing AR in first kidney recipients of living donors in TAC-based triple immunosuppression.
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Opportunistic infections occurring in renal transplant recipients in tropical countries p. 110
Krishan Lal Gupta, Sahil Bagai, Kiran Joshi, Manish Rathi, Harbir Singh Kohli, Vivekanand Jha, Vinay Sakhuja, Ashish Sharma, Mukut Minz, Arunaloke Chakrabarti
DOI:10.4103/ijot.ijot_47_18  
Introduction: Renal transplant recipients now have better graft survival rates, but continue to develop opportunistic infections. The present study was aimed at finding the incidence of opportunistic infections in the tropical environment in live-related transplant recipients. Materials and Methods: The study was carried out retrospectively with the help of medical records at a tertiary care hospital in North India from 2006 to 2010. The demographic and transplant details were noted, and data were analyzed for any possible risk factor. Results: A total of 1270 patients were studied, of which 231 infectious episodes were detected in 196 (15.4%) patients. Within 1 month, 11.7% of patients had infection, whereas 68.4% of patients had at least one infectious episode within the first 6 months of transplant. Bacterial infection (5.9%) followed by tuberculosis (4.9%), viral (3.8%), and fungal (2.1%) were the infections encountered. Aspergillosis (32.1%) was the most common fungal infection, followed by candidiasis and mucormycosis. The most common site of involvement was lung (26.4%), followed by urinary tract (13.0%). The overall patient survival was nearly 90%. Only 20% of patients had functional graft on follow-up in whom the graft was directly involved by a particular infection. Conclusions: Posttransplant infections continue to affect graft and patient survival. Higher rates are seen in the first 6 months posttransplant.
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Comparison of differential function of both kidneys in a healthy renal donor p. 115
Manish Gupta, Bharat Khadav, HL Gupta, TC Sadasukhi
DOI:10.4103/ijot.ijot_79_18  
Background: End Stage Renal Disease or Renal Failure demands a Renal transplant for fruitful propagation of life. People can donate one of their two kidneys, and the remaining kidney is able to perform the necessary functions. Living-kidney donation is the most common type of living-donor procedure. But it has still to be ascertained which of the two is a better functional kidney amongst the two in a general healthy population. Aim and Objective: Our study aims to answer the same here i.e to Identify the better functioning kidney amongst the two in a healthy Renal Donor on the basis of DTPA Scaning. Materials and Methods: Ours was a observational study in which data was collected from the 398 patients who underwent donor nephrectomy at our institute from January 2014 to December 2017. A comparison of their DTPA scans was made and the results were evaluated. Results: Out of the 398 patients 298 were female and 100 were male donors. 39% of the donors evaluated had a differential function difference in the range of 0-5 percent. In both, men and women, the differential function steadily decreased with progress in age and was found to be statistically significant in both right and left kidneys. Conclusion: The main aim of our study was to find out the better functioning kidney amongst the two. And with the help of statistical analysis we were able to adjudge the right kidney a better functioning one.
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Use of everolimus as an alternative to calcineurin inhibitors in renal allograft recipients: A single South Indian center's experience p. 118
Manns Manohar John, Mahesh Eswarappa, Gurudev K Chennabasappa, Gireesh M Siddiah, R Rajashekar, Vivek Gaurav
DOI:10.4103/ijot.ijot_74_18  
Introduction: Chronic Renal Allograft Injury(CRAI) is the most important cause of chronic graft dysfunction and loss. Calcineurin inhibitors (CNI) have been the back bone for immunosuppressive therapy, but their adverse effects can directly contribute to CRAI and compromise long-term renal allograft outcomes. Hence alternatives for CNI's such as Everolimus have been tried. Methods: Thirty de novo renal transplant patients who are receiving Everolimus as a part of their immunosuppressive regimen were included in this study. These patients were followed up for a period of 2 years. The primary outcome measures were creatinine clearance and the proportion of patients with biopsy proven acute rejection (BPAR). Results: Twenty three out of thirty patients were men. Follow up after initiation of everolimus the minimum duration was 2 years and maximum was of 5 years. There was a statically significant reduction in creatinine and improvement in GFR after initiation of everolimus to 3rd month of therapy and the reduction was consistent throughout the period of follow up which is for 24 months. Incidence of biopsy proven acute rejection (BPAR) was 16.7 %. Incidence of NODAT (New Onset Diabetes After Transplant) was 16.7. None of the patients had nephrotic range of proteinuria. Conclusions: Our study clearly shows use of everolimus is associated with improvement and subsequent stabilisation of graft function after switching over from CNI, without increased risk of BPAR and is associated with fewer adverse effects. Everolimus is a promising agent which can be used as an alternative/ additive agent in our immunosuppressive drugs regimens.
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Utility of plasma exchange in early recurrent C3 glomerulopathy p. 122
Ashwani Kumar, Joyita Bharati, Ritambhra Nada, Sarbpreet Singh, Ashish Sharma, Krishan Lal Gupta, Raja Ramachandran
DOI:10.4103/ijot.ijot_78_18  
Introduction: Treatment options for recurrent C3 glomerulopathy (C3G) are not explored in large trials. Only Eculizumab has been successfully used to improve the renal function in patients with recurrent C3G. In the current report, we are sharing our experience with plasma exchange (PLEX) in the management of early recurrent C3G post-renal transplantation. Materials and Methods: A total of four patients underwent PLEX. Time to recur was less than two weeks in all the patients. Serology levels, autoantibody testing and limited genetic workup was done in all the four patients. The clinical details of patients were recorded. Results: All the patients underwent 5 PLEX (40 ml/kg/session) with fresh frozen plasma as the replacement. The median time for post-transplant recurrence was 3-days. Immediate reduction in serum creatinine was seen in three (75%) patients. After a median last follow-up of 8.5 (range: 4-18) months, two (50%) patients achieved remission and the other two (50%) had resistant disease resulting in graft loss. Three patients tested positive for autoantibodies (two cases had positive C3-nephritic factor and one had anti-complement factor-H autoantibodies. Complement factor H gene analysis revealed rs1061170; p.His402Tyr (missense variant), rs1061147; p.Ala307= (synonymous variant) and rs2274700; p.Ala473= (synonymous variant) in three cases. All the three patients who had immediate response to PLEX had positive autoantibodies against complement pathway regulators. Conclusion: In the present report, we performed extensive workup for complement pathway abnormality and found that patients with recurrent C3G following transplantation having autoantibodies benefited with PLEX.
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CASE REPORTS Top

Multidrug-resistant coinfection and emphysematous pyelonephritis in a deceased donor allograft – Treatment dilemma p. 127
Sneha Haridas Anupama, Georgi Abraham, Milly Mathew, Anusha Rohit, Abraham Kurien
DOI:10.4103/ijot.ijot_57_18  
Emphysematous pyelonephritis (EPN) is a severe, potentially fatal suppurative infection of the renal parenchyma and perirenal tissues. It is indicated by the production of gas within the kidney and perinephric tissues. Risk factors that contribute to the development include diabetes and female sex. Herein, we report EPN in a 59-year-old male who underwent renal transplant from a deceased donor earlier this year.
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Graft-versus-host disease: Rare complication postliver transplant p. 130
Nivedita Pandey, Bhavna Bansal, Akash Jaiswal, Subhash Gupta
DOI:10.4103/ijot.ijot_71_18  
Graft-versus-host disease (GVHD) following liver transplantation (LT) is an uncommon complication but has high mortality and represents a major diagnostic challenge. A 63-year-old male with nonalcoholic steatohepatitis-related decompensated cirrhosis underwent deceased donor LT. His postoperative course was complicated by fever, diarrhea, skin rashes, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the duodenum and skin were consistent with acute GVHD. This was confirmed by chimerism study performed on the bone marrow. The patient was treated with basiliximab, corticosteroids, tacrolimus, and mycophenolate; however, he had minimal response to intensive immunosuppressive therapy. The patient died due to multiorgan failure.
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Brain abscess in a kidney transplant recipient due to an unusual fungal infection: A case report and review p. 134
Sahil Bagai, Krishan Lal Gupta, Rajesh Chhabra, Arunaloke Chakrabarti, Raja Ramachandran, Vivek Kumar, Manish Rathi, Harbir Singh Kohli, Ashish Sharma
DOI:10.4103/ijot.ijot_65_18  
Invasive mycosis is a serious complication of solid organ transplantation. Fungal infections even if appropriately diagnosed and treated with current antifungal agents, have a high mortality rate. A high index of suspicion is required and an attempt should be made to confirm the microbiological diagnosis from each site involved to rule out multiple infections. We report here a 41-year-old allograft recipient, who presented with fever associated with chills and one episode of generalized tonic clonic seizure 1-year post transplantation. Neuroimaging revealed a brain abscess, stereotactic biopsy from which yielded Scedosporium apiospermum on fungal culture. Whole blood quantitative cytomegalovirus (CMV) polymerase chain reaction done was positive. He also developed pulmonary aspergillosis and secondary hemophagocytosis later in the course of his hospital stay. His tacrolimus and mycophenolate were stopped and he was managed with i.v ganciclovir, amphoterecin b, voriconazole, high dose i.v immunoglobulins and surgical draingae of abscess. With all measures, he showed improvement in his general and neurological condition and maintained good graft function. Scedosporium is a rare cause of brain abscess. CMV co-infection leads to increased chances of other opportunistic infections. Good microbiological workup from each site involved in immunosuppressed subjects is the need of the hour as early diagnosis can lead to lesser mortality and morbidity.
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Disseminated cutaneous cryptococcal infection in kidney transplant recipient p. 138
Suhas Dilip Mondhe, Girish Vasudeo Kumthekar, Santosh Hedau, P Vikranth Reddy, Srikanth Gundlapalli
DOI:10.4103/ijot.ijot_58_18  
Postkidney transplant infectious complications are always challenging due to atypical organisms, varied presentation, and the balanced treatment to avoid rejection. They are often fatal if not diagnosed and treated in time. High clinical suspicion and decreasing immunosuppression are the important points to remember. This is a case report of postkidney transplant recipient with disseminated cryptococcal infection. The patient improved with functioning graft with appropriate antifungal treatment.
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Late-onset posttransplant lymphoproliferative disease in a male kidney transplant patient on minimal triple immunosuppressive therapy: Diagnosis and management p. 141
Sneha Haridas Anupama, Milly Mathew, Victorine Bandolo, Priyanka Koshy, Georgi Abraham
DOI:10.4103/ijot.ijot_56_18  
A 57-year-old male who had a successful live-related renal transplantation 14 years ago with stable graft function, on minimal triple immunosupression, presented with Burkholderia cepecia septicemia and graft dysfunction. He was successfully treated with parenteral imepenam. He was found to be Epstein–Barr virus Immunoglobulin G seropositive. Positron-emission tomography scan done showed metabolically active multiple cervical, mediastinal, axillary retroperitoneal, mesenteric, iliac, and inguinal lymphadenopathy. Further investigations revealed polymorphic posttransplant lymphoproliferative disease. His immunosuppressive therapy was tailored to lower cyclosporine dosage and discontinuation of azathioprine. His renal function improved. He was diagnosed to have a T-cell non-Hodgkin's lymphoma and subsequently succumbed to sepsis.
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Successful management of a rare complication after percutaneous transplanted kidney biopsy p. 145
Suraj Godara, Jitesh Jeswani, Nipun Gumber
DOI:10.4103/ijot.ijot_85_18  
Renal hematoma is the most commonly reported complications after percutaneous renal biopsies, but fortunately, these are self-limited in most of the cases with no need for active intervention. Other complications such as arteriovenous fistula, colonic injury, infections, or pneumothorax are much less frequent life-threatening, and stated to occur in <0.1% of cases. We describe a case in which percutaneous renal biopsy is complicated by subcapsular hematoma due to tamponade following which the patient underwent surgical intervention. Although uncommon, sub capsular hematoma may be fatal and requires early intervention to save the graft kidney.
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Combination of clindamycin and primaquine for Pneumocystis pneumonia in renal transplant recipients p. 147
Mohammed Shoeb Ahmed Khan, VN Unni, K Vinod Kumar, PK Bipi, P Jojo
DOI:10.4103/ijot.ijot_72_18  
Pneumocystis pneumonia (PCP) in kidney transplant recipients is usually treated with trimethoprim-sulfamethoxazole (TMP-SMX). Combination of clindamycin and primaquine (C + P) is recommended for treatment failure. Data are scarce for treatment with C + P in renal transplant recipients. Here, we present three kidney transplant recipients on triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone) diagnosed to have PCP at different time periods after transplant surgery. Bronchoscopy and lavage were done; special staining with Gomori methenamine silver stain demonstrated Pneumocystis jirovecii. Two patients had graft dysfunction at the time of diagnosis. The first patient was started on TMP-SMX but developed leukopenia and was started on oral C + P. The other two cases had graft dysfunction and were started on C + P. All responded to therapy without complications, and improvement in graft function was observed. Clindamycin with primaquine can be considered as a safe and effective option to treat PCP in renal transplant recipients; this combination can replace TMP-SMX, as the first-line therapy, especially in patients with graft dysfunction or leukopenia
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