Unrelated Kidney Transplantation Research Articles

Fibronectin glomerulopathy in a kidney allograft biopsy

BackgroundFibronectin glomerulopathy is a rare genetic nephropathy with only a few cases of post-transplant recurrence being reported previously. We highlight a case that was initially misdiagnosed and emphasize the importance of full immunofluorescence and electron microscopy evaluation in allograft biopsies.Case presentationA 36-year-old male with a history of end-stage kidney disease secondary to biopsy-proven type 1 membranoproliferative glomerulonephritis (MPGN) status-post living unrelated donor kidney transplant 12 years prior, presented with increasing creatinine and proteinuria. Biopsy was performed and was consistent with fibronectin glomerulopathy. Subsequent genetic testing revealed an FN1 mutation, the primary gene associated with this condition.ConclusionsFull histologic evaluation of the allograft biopsy corrected the diagnosis and additionally suggested that the patient's mother, who had expired in her 30s and had received a diagnosis of type 1 MPGN on autopsy, likely also had fibronectin glomerulopathy, enabling appropriate genetic counseling for the family.

A Case Report of Successful Renal Transplantation After Surgically Treated Type A Aortic Dissection

BackgroundAortoiliac lesions can influence the results of kidney transplantation and increase technical difficulties during surgery. Aortic dissection (AD) is a rare and infrequently reported event before transplantation, whereas immediate optimal perfusion is paramount for kidney transplantation. Thus, adequate blood flow imposed by the flow from the true lumen must be considered when choosing a target inflow vessel. Case presentationA 67-year-old man on dialysis with end-stage renal disease caused by immunoglobulin A nephropathy was referred for kidney transplantation. He had successfully undergone conventional Stanford type A AD surgery 3 years ago. Pretransplant contrast-enhanced computed tomography angiography revealed termination of the distal intimal flaps within the common iliac arteries. Dilation of the descending aorta was also observed. Based on the meticulous vascular assessment, including consultation with the cardiovascular surgery department, the right internal iliac artery (IIA) was considered usable for anastomosis. He underwent living unrelated kidney transplantation from his 66-year-old wife. The patency and blood flow in the right IIA were also verified using intraoperative findings. Without any special procedure, we used a side-to-end arterial anastomosis between the donor renal artery and recipient IIA. After vascular clamp removal, the allograft was perfused homogeneously and immediately functioned. ConclusionPatients receiving previous surgery for type A AD can successfully undergo kidney transplantation if the patency of the iliac arteries from the true lumen is confirmed by perioperative evaluation, and the artery can be carefully clamped to avoid possible further dissection.

A RARE PRESENTATION OF MYCOPHENOLATE MOFETIL-INDUCED SEGMENTAL COLITIS MASQUERADING AS ISCHEMIC COLITIS

Abstract Mycophenolate mofetil (MMOF) is an immunosuppressive pro-drug commonly used to prevent rejection in recipients of solid organ transplants. It is hepatically converted to mycophenolic acid which then acts to reversibly inhibit inosine monophosphate dehydrogenase, thereby preventing B and T lymphocyte proliferation, B cell antibody formation, and leukocyte recruitment to sites of inflammation. Diarrhea is the most common gastrointestinal side effect of MMOF usage with up to 40% of renal transplant patients on MMOF reporting this symptom and colonoscopy not infrequently shows injurious changes that range from edema and erythema to ulcerations and diffuse colitis. Isolated reports note that colonic histopathology from patients on MMOF sometimes mimic graft-versus-host disease, inflammatory bowel disease, or ischemic colitis. However, there are very few cases that describe segmental colitis in MMOF patients. We present a rare case of a renal transplant patient presenting with MMOF-induced segmental colitis after 4 years of medication usage. A 52-year-old male with a history of native kidney end stage renal disease secondary to diabetic nephrosclerosis status post living unrelated kidney transplant 4 years ago from his wife presented to the emergency room for 1 week of intractable abdominal pain, vomiting, and diarrhea. His current transplant medications included atovaquone, tacrolimus, and mycophenolate mofetil. Lab work showed chronic pancytopenia with hemoglobin 10, MCV 85, platelets 58, BUN:Cr 87:5.6, and tacrolimus level 34.8. His last colonoscopy 7 years ago was unremarkable and the patient had never had an esophagogastroduodenoscopy (EGD) before. EGD while admitted showed significant erosive gastropathy with pathology showing the same. Sigmoidoscopy showed segmental colitis with punctate erythema and loss of vascularity up to the splenic flexure with the distribution of mucosal disruption suggestive of ischemic colitis. Histopathology showed fragments of colonic mucosa with patchy active cryptitis, surface erosion, distorted crypts with concurrent apoptosis and scattered eosinophils in the lamina propria – findings consistent with mycophenolate colitis. Symptomatic care was provided and the patient’s mycophenolate was tapered to cessation with complete resolution of symptoms. He was discharged with appropriate follow-up. Our case highlights a rare presentation of MMOF-induced injury whereby despite, appearance on endoscopy as a segmental ischemic colitis, histopathology was negative for ischemia but notable for MMOF-induced injury which was confirmed by symptom resolution following discontinuation of the immunosuppressive drug.. With early recognition of this pathology by clinicians with subsequent MMOF discontinuation, symptoms and prognosis can be remarkably improved. Colonoscopic image showing segmental colitis with punctate erythema and loss of vascularity. Fragments of colonic mucosa with patchy active cryptitis (star), surface erosion, mildly distorted crypts and apoptosis mainly in crypt bases with scattered eosinophils in the lamina propria, indicative of mycophenolate colitis. 400x magnification.

Unrelated versus related living-donor kidney transplantation is associated with higher acute rejection rate but similar graft survival Running title: Outcomes in living-donor kidney transplantation

Kidney transplantation (KT) from living donors has been shown to have multiple benefits compared with that from deceased donors. We sought to compare significant graft outcomes, namely acute rejection (AR), graft function, and survival, between transplant recipients who received a kidney from a living-related donor (LRD) and from a living unrelated donor (LURD). Our cohort comprised 198 donor and recipient pairs undergoing living-donor KT at our center over 10 years. LRD recipients were compared with LURD recipients according to demographic and clinical characteristics, transplant variables (including immunosuppression), graft function, survival, and AR rate. The estimated glomerular filtration rate (eGFR) was similar in both groups over the follow-up time, of 60-65 mL/min (p<0.05 over a 10-year period). Censored graft survival was similar between LRD and LURD recipients (96.9% vs. 98.0% at 5 years and 87.8% vs. 79.4% at 10 years, respectively; p=0.837). LURD recipients had a higher incidence of AR, although LURD recipient status was not an independent risk factor for AR. Multivariate analysis showed that human leukocyte antigen (HLA) -DR mismatch (MM) was an independent predictor of AR (hazard ratio [HR] 2.256, p<0.05). HLA-A and HLA-B MM did not affect the AR HR between the groups. Graft function and censored-death survival rates were similar between the LURD and LRD KT recipients. HLA-DR MM was an independent risk factor for AR.

413.4: The Beginning of the End for Living Unrelated Donation Kidney Transplantations in the Middle East: The Shiraz Transplant Center Experience

Background: The Middle East is a region with much controversy and limitations regarding deceased organ transplantations. In this report we describe our unique experience with the establishment of our deceased donor organ donation program for Central and Southern Iran. Methods: During the initial phases in the 70s and 80s, only living related kidney transplantations were allowed in Iran. However, this policy was not continued and was expanded due to severe shortage of hemodialysis facilities and an urgent need to increase the number of kidney transplantations. Accordingly, some centers in Tehran started unrelated kidney transplantation with the support of the government that offered bonuses to persuade unrelated donors. It should be mentioned that, during this time, permission for deceased organ donation was not yet obtained in Iran. The main focus of the Shiraz Transplant Center was to develop a deceased donation program from the beginning. During three decades this center was able to expand its deceased donation program to a degree that in 2008 it completely replaced all its unrelated kidney donations by deceased donations. Prior to 2008, most transplantations were related living and deceased donations, and only in cases where a patient was on the wait list for more than one year and a compatible donor was not found, they were only allowed to have living unrelated donations. The deceased program in the STC has since expanded and has aimed to stop unrelated living donations to achieve some goals which include: to abide by ethical guidelines in organ donations/transplantation such as the declaration of Istanbul, and to finally change the dominant practice of unrelated living donations within the Middle East. These efforts have resulted in an increase of deceased donations in Iran from 1.6 in 2004 to 14.34 per million population in 2019, and in some areas this has reached to as high as 50. Results: Up to March 2021, in the STC, overall 5389 kidney transplantations have been performed. Figure 1 shows the trend in kidney transplantation in the STC. Conclusion: Living unrelated donations are still an ongoing issue in the Middle East region. Our center, has implemented a wide deceased donor program and as a result has been able to completely stop unrelated living kidney transplantations. The deceased donor organ donation program should further be expanded within Iran and other countries in the region and continuous campaigns should be held up against any type of unethical issues such as living unrelated transplantations to meet with international standards.

P8.057: Cannabidiol (CBD) Oil and Tacrolimus: The Unexpected High in Renal Transplant Recipients – Case Series and Review

Introduction: Calcineurin inhibitor (CNI) based regimens afford the greatest protection against acute rejection and are used in > 90% of kidney transplant recipients. Cannabidiol (CBD) has been advertised as a natural remedy to treat several disorders. Information on the concurrent use of CBD and tacrolimus is limited. Herein we describe four cases of patients reporting CBD use post kidney transplant, and the effects on tacrolimus drug levels. Results: □Case 1: 38-year-old male with chronic kidney disease secondary to polycystic kidney disease (PKD) received a living unrelated kidney transplant from his spouse.His course was uncomplicated until 3 months post-transplant when he started using CBD oil for sleep. One week after starting CBD oil he presented for follow up and was noted to have a tacrolimus level of 40.1 ng/mL. His tacrolimus level returned at 20 ng/mL after stopping CBD oil. □Case2: A 55-year-old male with chronic kidney disease secondary to lithium toxicity received a living unrelated kidney transplant. He self-started CBD oil three weeks post-transplant and was noted to have an increase in tacrolimus level to 16.1 ng/mLHe elected to stop his CBD oil because he thought it may be interfering with his medications and four days later his tacrolimus levels decreased to 8.8 ng/mL. □Case3: 46 year old male with ESRD ascribed to diabetes mellitus received a deceased donor kidney transplant.One year later he presented for a routine follow up with a serum creatinine of 3.7 mg/dL with a tacrolimus level of 2.4 ng/mLHe reported taking CBD oil for the past 6 weeks for anxiety.His tacrolimus was increased, and he underwent a kidney transplant biopsy which showed acute cell mediated and vascular rejection with chronic active antibody mediated rejection. HLA testing showed de novo HLA antibodies to DQ7 and DQA1*05. □Case 4: 64 yr old female received her pancreas transplant in 2005.14 years later patient presented for a routine follow up and was noticed to have a tacrolimus level of 12.1 while on a steady dose of 1 mg BID. She endorsed starting CBD oil a month prior for relief of her neuropathy symptoms.Her tacrolimus was adjusted down to 0.5 mg BID with improvement inher level to 7. Discussion: Cannabidiol (CBD) is a non-psychogenic cannabinoid found in the Cannibis sativa plant. The Agriculture Improvement Act of 2018 legalized production of industrial hemp plants, so long as it contained no more than 0.3% of delta-9-tetrahydrocannabinol (THC).Interestingly, amongst our cases 3 resulted in an increase in tacrolimus levels and another resulted in a marked decrease in tacrolimus levels which precipitated allograft rejection. all cases of increased levels occurred without a change in tacrolimus dosing and relative stable levels prior to known administration. Tacrolimus levels improved after stopping CBD oil supplements. The solitary case of reduced tacrolimus levels following CBD oil exposure i may have been related to another compound within the CBD oil labelled product.

Living Kidney Donation Criteria of Baskent University.

Kidney transplant is the best treatment for patients with end-stage renal disease. Preparation of living related kidney donors and recipients is the major step to achieve their best long-term outcomes. Here, we present the Baskent University criteria for living kidney donors and recipients. The Baskent team has performed >2000 kidney transplants from 1985 to 2022 under leadership of Prof. Mehmet Haberal, a transplantation pioneer in Turkey, who facilitated Turkish legislation on procurement, storage, engraftment, and transplant of organs and tissues in June 1979, which has been adopted in other countries with few changes. Although the main frame is similar, we have constant principles in kidney donation. Baskent University is now known as an exceptional transplant center in Turkey, the Middle East, Europe, and the world and has established its own donor criteria for both kidney and liver transplant. Volunteerism remains a core principle of living kidney donation, regardless of other criteria. At Baskent University, donor protection from social, psychological, and health problems is paramount. Loss-profit and risk of transplant are assessed for every case. Donors must be followed up and remedies sought for failed criteria. Dr. Haberal's principles are the basis of Baskent University donation criteria, and unrelated kidney transplant donors are accepted only in cases of cross-donation. Major distinctions of Baskent University's living related donor criteria are (1) absence of unrelated or nondirected donation, (2) lowest acceptable donor glomerular filtration rate of 100 mL/min, (3) rejection of hypertensive donor candidates (regardless of medication), and (4) obesity must be corrected before transplant if body mass index (measured as body weight in kilograms divided by height in meters squared) is >30. The Baskent University donor selection criteria provide excellent long-term outcomes of kidney donors that have been proved by our recent studies.

Outcomes of living unrelated donor kidney transplants in children: An Organ Procurement and Transplant Network database analysis.

There are conflicting data on long-term outcomes of pediatric LURD renal Txs compared to Txs of kidneys from other donor sources. An analysis of the OPTN database was conducted in children (<18 years) who had received their 1st kidney-only Tx between January 1, 2000, and September 30, 2021. The primary outcome measure was time to graft failure or death. Cox event history regression model for time to primary outcome, categorized by donor source and adjusting for confounders was performed. Of the 12 089 subjects, 327 (2.7%) received kidneys from LURDs, 4349 (36%) from LRDs and 7413 (61%) from DD. One year graft failure rate was 3.56%. On regression analyses, compared to LRD kidney recipients, LURD recipients had comparable graft survival (graft failure AHR 1.15, 95th percentile confidence interval 0.87-1.51; p .31) and DD recipients had lower graft survival (graft failure hazard ratio 1.26, 95th percentile confidence interval 1.10-1.43; p < .001). When using living unrelated kidney recipients as the reference group, DD kidney recipients had comparable graft survival, with a wide confidence interval (hazard ratio for graft failure 1.09; 0.83-1.43, p .53). Pediatric LURD kidney recipients have comparable graft survival to LRD kidney recipients; DD kidney recipients had the poorest survival. Our study, the largest to date, should encourage centers to embrace non-commercial living-unrelated transplantation as a viable option for children, preferable to DD kidneys.

Reversed diastolic flow in a renal transplant due to ureteric obstruction from intraluminal blood clot

AbstractReversal of arterial diastolic flow is commonly considered a sign of transplant renal vein thrombosis until proven otherwise, with the differential including acute rejection, acute tubular necrosis, and perirenal hematoma. We discuss a case of a patient who presented with decreased urine output on the second postoperative day following living unrelated kidney transplantation. Doppler ultrasound was performed and demonstrated reversal of diastolic flow in the transplant renal artery. Prompt surgical exploration revealed intraluminal blood clot obstructing the ureter. To our knowledge, this is the first reported case of reversed diastolic flow secondary to ureteral obstruction by an intraluminal blood clot.

POS-692 Euglycemic Diabetic Ketoacidosis Related to SGLT2 Inhibitor Use in Kidney Transplant Patient with Squamous Cell Carcinoma

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have renal protective effect in diabetic and non-diabetic patients with significant reduction of cardiovascular events. The data is emerging for the short-term efficacy and safety of SGLT2 inhibitor in diabetic kidney transplant patients. Diabetic ketoacidosis is a well recognized side effect of SGLT2i with variable predisposing factors. There is limited data regarding the use of SGLT2i in oncology patients. We described a case of diabetic kidney transplant patient on dapagliflozin who developed DKA during active therapy for squamous cell carcinoma. A 65 years old female, known to have hypertension and diabetes mellitus type 2 leading to end stage renal disease. She underwent living unrelated kidney transplantation in 2018. Her home medications included insulin glargine, dapagliflozin 10 mg, pantoprazole 40mg, prednisolone 7.5 mg daily, cyclosporine 125 mg q12 hours and atorvastatin 20mg. She was diagnosed with right inner cheek moderately differentiated keratinizing squamous cell carcinoma with submandibular lymphadenopathy (Stage: cT4aN2M0). She was initiated on concurrent chemotherapy (Cetuximab) and radiotherapy. Cycle 4 of therapy was complicated with poor oral intake and severe mucositis for 3 days prior to admission. She had evidence of acute kidney injury stage 1 in transplanted kidney (serum creatinine increased from baseline of 58 to 110 micromole/l). Other laboratory investigations revealed hyperkalemia 5.7mmol/l, metabolic acidosis 6mmol/l, high anion gap metabolic acidosis, normal lactate level, arterial PH of 7.1, ketones were positive in urine and blood glucose level of 12mmol/l. She was diagnosed with severe euglycemic diabetic ketoacidosis DKA, due to SGLT2i (dapagliflozin 10 mg) and starvation. She required critical care admission with rigorous IV hydration, insulin infusion per DKA protocol, IV sodium bicarbonate, IV hydrocortisone and IV cyclosporine. Her clinical condition improved by fifth day of critical care. Urinary tract infection and re-feeding syndrome post nasogastric enteral feeding complicated her hospital course. Dapagliflozin was held and next cycle of chemo-radiotherapy was delayed. Some of the potential risk factors for euglycemic DKA induced by SGLT2 inhibitors are infections, withdrawal of insulin, starvation, dehydration and acute kidney injury. The underlying pathophysiologic process of ketoacidosis induced by SGLT2 inhibitors is not well established. There are few case reports describing this complication in diabetic oncology patients, leading to discontinuation of the drug. The use of SGLT2 inhibitor is limited in diabetic kidney transplant patients and about 100 cases reported in literature without evidence of DKA in short-term follow up. To the best of our knowledge, this is the first case describing a successful management of dapagliflozin-induced euglycemic DKA in kidney transplant patient with squamous cell carcinoma. SGLT2 inhibitor associated eDKA is very rare in oncology patients and this is the first case reported in kidney transplant patient who was on active chemotherapy and radiotherapy for squamous cell carcinoma. We suggest to hold SGLT2i therapy during active oncology treatment especially in the setting on severe mucositis.

Utility of Serial Donor-derived Cell-free DNA Measurements for Detecting Allograft Rejection in a Kidney Transplant Recipient After PD-1 Checkpoint Inhibitor Administration

Background.Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker of rejection that originates from allograft cells undergoing injury. Plasma levels <1% in kidney transplant recipients have a high negative predictive value for active allograft rejection. The utility of this biomarker in kidney transplant recipients receiving immune checkpoint inhibitor therapy is unknown.Methods.We describe a case in which serial dd-cfDNA monitoring facilitated the use of immune checkpoint inhibitor therapy, which is known to be associated with high rates of rejection, in a kidney transplant recipient with metastatic cancer.Results.A 72-y-old man with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease underwent living unrelated kidney transplant in December 2010. His immunosuppression regimen included tacrolimus, mycophenolate, and prednisone. In July 2017, he presented with metastatic cutaneous squamous cell carcinoma. After his disease progressed through radiation therapy and cetuximab, he received pembrolizumab (antiprogrammed cell death protein 1). His dd-cfDNA level was undetectable at baseline, then increased during treatment but remained <1%. This trend, despite fluctuations in serum creatinine levels during therapy, allowed for continuation of pembrolizumab and successful treatment of his metastatic cancer without clinically evident allograft rejection. After discontinuation of pembrolizumab, dd-cfDNA levels fell below the level of detection. Genetic analysis of the cutaneous squamous cell carcinoma demonstrated a genetic profile distinct from the dd-cfDNA, indicating that tumor lysis did not impact increases in dd-cfDNA.Conclusions.Serial dd-cfDNA measurements may provide a useful, noninvasive biomarker for detecting allograft injury that may facilitate the use of immunomodulatory therapies in organ transplant recipients with cancer.

Effect of the similarity of gut microbiota composition between donor and recipient on graft function after living donor kidney transplantation

Graft outcomes of unrelated donor kidney transplant are comparable with those of related donor kidney transplant despite their genetic distance. This study aimed to identify whether the similarity of donor–recipient gut microbiota composition affects early transplant outcomes. Stool samples from 67 pairs of kidney transplant recipients and donors were collected. Gut microbiota differences between donors and recipients were determined using weighted UniFrac distance. Among the donor–recipient pairs, 30 (44.8%) pairs were related, while 37 (55.2%) were unrelated. The unrelated pairs, especially spousal pairs, had similar microbial composition, and they more frequently shared their meals than related pairs did. The weighted UniFrac distance showed an inverse correlation with the 6-month allograft function (p = 0.034); the correlation was significant in the unrelated pairs (p = 0.003). In the unrelated pairs, the microbial distance showed an excellent accuracy in predicting the estimated glomerular filtration rate of < 60 mL/min/1.73 m2 at 6-months post-transplantation and was better than human leukocyte antigen incompatibility and rejection. The incidence of infection within 6 months post-transplantation increased in the recipients having dissimilar microbiota with donors compared to the other recipients. Thus, pre-transplantation microbial similarity in unrelated donors and recipients may be associated with 6-month allograft function.

COMPARISON OF CLINICAL OUTCOMES OF LIVING DONOR KIDNEY TRANSPLANTATION IN FEMALE RECIPIENTS WITH BIRTH HISTORY ACCORDING TO THE RELATION TO A DONOR

Live-donor kidney transplantation has significantly increased the size of the donor pool, and live-unrelated kidney transplantation, especially spousal donation has increased exponentially. Living unrelated and related kidney transplantation has been shown to have similar allograft survival. However, the effect of donor-recipient relationship in living-related and unrelated kidney transplantation on graft and patient survival remains uncertain. Thus, the aim of this study was to evaluate the effect of live-donor types and graft outcomes. From January 2009 to January 2018, a total of 2,680 kidney transplants were performed at Asan Medical Center, while 2,060 living donor kidney transplantations were performed. We studied 864 female recipients from living donors with pregnancy history, and HLA-incompatible, retransplantation and those without or unknown pregnancy history were excluded. The female recipients were categorized into three groups; Offspring-to-mother (Group I), husband-to-wife (Group II), and other unrelated donors (Group III). The primary endpoint of this study was biopsy-proven acute rejection and graft survival. We also evaluated delayed graft function (DGF), death-censored graft failure and mortality. Number of HLA ABDR mismatch was significantly lower in group I and there were more ABO incompatible kidney transplantation in group II compared to the other groups. There were 4 (2.3%), 3 (1.9%), and 3 (5.4%) cases of mortality in group I, group II, and group III, respectively (p= 0.352). There was no significant difference in the one, three, and five years patient survival among groups (p=0.444). There was no significant difference in the biopsy-proven acute rejection between the three groups. Clinical rejection and DGF occurred at a high rate in group II compared to group I and group III, but there was no statistically significant difference between the three groups. We conclude that both offspring and spousal living donor transplants have similar patient and graft survival and can be considered whenever feasible for female recipients with multiple donor options.

P0647ACUTE KIDNEY INJURY SECONDARY TO SUCROSE CONTAING INTAVENOUS IMMUNOGLOBULIN

Abstract Background and Aims Intravenous immunoglobulins (IVIG) are pooled polyvalent IgG antibodies extracted from the human plasma. While the initial indications were mainly immune deficiency states and some autoimmune diseases, the usage has been widened to include several immune mediated diseases, viral infections, and organ transplant rejection. Stabilizers in IVIG may include sugars, such as sucrose, glucose, or maltose. Sucrose in IVIG preparations may cause acute kidney injury. We report the case of a renal transplant patient who developed acute kidney injury due to sucrose nephropathy following the administration of sucrose containing IVIG. Method Four months after transplantation he was referred to our Hospital for deterioration of kidney function with eGFR (by MDRD formula) of 27ml/min. Cytomegalovirus virus (CMV) PCR turned positive (3300 copies/ml). Cyclosporine levels were high (C2: 2937 ng/ml) and hence, cyclosporine dose was adjusted. Induction therapy with Injection Ganciclovir for 2 weeks, followed by therapeutic dose of oral Valganciclovir was administered for the treatment of CMV infection. Skin examination revealed annular purple patches, suspicious of Kaposi Sarcoma, on the upper limbs. Skin biopsy confirmed the diagnosis. It was planned to give total IVIG of 2 gm/ kg in four daily divided doses. After completion of the second dose, serum creatinine increased to 370 µmol/L. He was clinically asymptomatic, euvolumic, vital signs were stable, and his urine output remained normal and his urinalysis was inactive. Results The ultrasound of the transplant kidney was normal with normal resistivity index. IVIG was stopped. He was well hydrated and underwent ultrasound guided biopsy. The graft biopsy showed acute tubular injury with flattening and vacuolation of tubular epithelial cells. Mitosis indicating tubular regeneration was seen. There was mild focal interstitial inflammation (20%) with mild lymphocytic tubulitis not amounting to graft rejection. Immunohistochemistry for C4d and polyomavirus (BKV) were both negative. The features were most consistent with sucrose induced nephropathy (Figure 1). Subsequent visits showed a decrease in BKV-PCR serum level and eventually undetected serum level of BKV-PCR at follow up about a month later. Conclusion In this paper, we presented a case of a living unrelated kidney transplant recipient who developed BKV nephropathy and developed impaired kidney function. The patient also had new onset diabetes mellitus after kidney transplantation (NODAT) but was otherwise in good general health. Treatment included sucrose containing IVIG. The patient subsequently developed acute kidney injury. The outcome was favorable with recovery of filtration rate to the baseline within 21 days without the need for dialysis. We conclude that the administration of sucrose containing IVIG may lead to acute kidney injury. We recommend the use of sucrose-free IVIG whenever possible. In all cases, caution is required when administrating IVIG.

Treatment of parvovirus B19 viremia to facilitate kidney transplantation in a patient with collapsing glomerulopathy

Collapsing glomerulopathy (CG) is a severe form of glomerulopathy which results in nephrotic syndrome and often ensues in rapid progression to end-stage kidney disease (ESKD). Although most commonly a result of HIV infection, other conditions such as parvovirus B19 (PB19) infection have been associated with CG. We present a case of an 18-year-old male with CG associated with PB19 infection who was heterozygous for APOL1 G1 and G2 genetic variants. In an attempt to treat, he was started on intravenous immunoglobulin (IVIg), however rapidly progressed to ESKD. During workup for a living donor kidney transplant he was found to have persistent low-grade PB19 viremia. Despite having no major immunodeficiency and given subsequent courses of IVIg, viremia continued to persist. In a final attempt to eradicate the PB19 we began treatment with cidofovir, an antiviral agent with in vitro efficacy against PB19. Subsequent to initiation of cidofovir, PB19 viremia slowly cleared after which he received a living unrelated kidney transplant. The patient had an early cellular rejection treated with rabbit antithymocyte globulin after which he recovered kidney function without signs of recurrent CG. Our case report suggests efficacy of IVIg and cidofovir for persistent PB19 infection in ESKD to allow subsequent transplantation, while minimizing the risk of recurrent CG.

Relationship Between Osteoporosis and Serum Sclerostin Levels in Kidney Transplant Recipients.

Sclerostin, a peptide secreted primarily by osteocytes, suppresses osteoblast maturation, thus reducing bone formation. Here, we evaluated the relationship between sclerostin levels and osteoporosis in kidney transplant recipients. This cross-sectional study included 78 kidney transplantrecipients > 18 years old and at least 6 months posttransplant. In our center, unrelated living-donor kidney transplants are not performed. Patients with parathyroid adenoma or parathyroidectomy history were excluded. Lumbar and femoral neck bone mineral densities andT and Z scores were obtained by dual-energy X-ray absorptiometry; results were used to divide patients into osteoporotic and nonosteoporotic groups. Serum sclerostin was measured by enzyme-linked immunosorbent assay. : Of total patients, 43% had osteoporosis, mean age was 40.8 years, and 70% were male. Groups had similar ages, male-female distribution, time posttransplant, cumulative corticosteroid dose, estimated glomerular filtration rates, and 25-hydroxyvitamin D2 levels (P > .05). The osteoporotic group had lower sclerostin (405.9 ± 234.9 vs 521.7 ± 233.5 ng/dL; P = .035) and higherintact parathyroid hormone levels (110.9 ± 68.0 vs 84.8 ± 41.4 pg/mL; P = .04) than the nonosteoporotic group. Sclerostin levels were not correlated with cumulative corticosteroid dose, intact parathyroid hormone, bone mineral density, and T scores at any site but were weakly negatively correlated with age (P = .04, r = -0.25). In multiple regression analyses, only intact parathyroid hormone had negative effects on lumbar bone mineral density (P = .02) andT scores (P = .036). Serum sclerostin levels, age, and cumulative corticosteroid dose did not affect lumbar or hip bone mineral density and T scores (P > .05). Sclerostin levels were low in our osteoporotic patients;therefore, sclerostin may not be a contributing factor to osteoporosis development. Because sclerostin is an osteocyte-derived peptide, its serum levels only reflect total osteocyte number and bone mass.

Retrospective genetic analysis illustrates the spectrum of autosomal Alport syndrome in a case of living-related donor kidney transplantation

BackgroundKidney transplantation is the treatment of choice in end-stage renal disease due to Alport syndrome (AS). However, the chances of finding an adequate living-related donor in AS are much worse compared to non-heritable conditions. Successful cases of related living-donor transplantation mostly refer to X-linked AS but are rarely reported in genetically confirmed autosomal AS.Case presentationWe describe the outcome of an exceptional AB0-incompatible kidney donation from father to son in a family with altered COL4A3. While decision-making was based on extensive clinical donor evaluation prior to transplantation, we analyzed the underlying genetic background in retrospect and associated these findings with the phenotype in all available family members. While biallelic COL4A3 variants caused autosomal recessive AS (ARAS) in the son (recipient), heterozygous family members, including the father (donor), showed minimal renal involvement and high-frequency sensorineural hearing impairment later in life indicating mild autosomal dominant Alport syndrome (ADAS). The recipient’s successful participation in the European and World Transplant Games is a testament to the positive outcome of transplantation.ConclusionsIn summary, living-related donor transplantation may be successful in autosomal AS, provided that thorough clinical and genetic evaluation of potential donors is performed. However, unrelated kidney transplantation should be given priority upon unpredictable genetic risk. Individual genetic variant interpretation is an important component of personalized donor assessment and will help to better predict genetic risk in the future.

Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft

BackgroundProliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of “Monoclonal gammopathy-related kidney diseases”, and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I).Case presentationThe patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant.ConclusionsIn a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.

Living Unrelated Kidney Transplantation: Does It Prevent Deceased-Donor Kidney Transplantation Growth?

It is usually assumed that an active livingdonor transplant program inhibits the growth of a deceased-donor kidney transplant program. In our 33-year experience, we found the contrary to be true. From 1984 until 2017, we performed a total of 4966 kidney transplant procedures. All cases were registered through the Collaborating Transplant Study (Heidelberg, Germany). During the first 16 years, only living-donor kidney transplant procedures were done. Our first unrelated living-donor kidney transplant procedure was in 1986 and involved a wife to husband donation. This breakthrough in our country was the first in our unrelated living-donor kidney transplant program. In 2000, the Iranian Parliament passed the deceased-donor transplant act, and we have started deceased-donor kidney transplants since then. Despite a jam-packed living-donor kidney transplant program, our deceased-donor kidney transplant program has grown steadily since then and now comprises more than 50% of our kidney transplant procedures. When we compared the outcome of these programs, the 5-year survival from Collaborating Transplant Study report of 3527 cases of 114 living-related donor procedures was 90%. The 5-year survival rates for living unrelated-donor (n = 2689) and deceased-donor (n = 724) transplant procedures were 88% and 83%, respectively (P = .001). Our data showed that deceased-donor kidney transplant procedures have steadily increased despite an active unrelated living-donor kidney transplant program. Wait lists for kidney transplant can be significantly reduced by following our model, both in developed and in developing countries.

Thrombotic Microangiopathy Complicating Cyclosporine in Renal Transplant Patients

Background and objectives: Experience with cyclosporine-associated thrombotic microangiopathy in renal allograft recipients is generally anecdotal; detailed descriptions of clinical behavior, therapeutic options and experience are also anecdotal and few. The aim of this study was to identify possible contributing factors to cyclosporine-associated thrombotic microangiopathy and to investigate therapeutic modifications that result in better graft survival in these patients. Methods: One thousand and twenty patients evaluated for this study received live-related or unrelated kidney transplants at Rizgary teaching hospital and Zheen international hospital between July 2011 and September 2016. The patients received standard induction therapy with anti-thymocyte globulin or basliximab and cyclosporine or mycophenplate and steroids. Regular follow-up with blood film and counts, reticulocyte count, liver enzymes, renal function tests, lactic dehydrogenas, haptoglobin and serum electrolytes were performed. Results: The prevalence of cyclosporine-associated thrombotic microangiopathy was 1.73%; of which 4(26.7%) were male while 11(73.3%) were female, with male to female ratio of 1:2.75. Mean age ±standard deviation of 36.87±10.927. Chronic glomerulonephritis was the most frequently distributed type of pre-transplant diagnosis 5 (33.3%), followed by focal segmental glomerulosclerosis 4 (26.7%) and diabetes mellitus 3 (20%). Live-related was the maximum frequent 10 (67%) while live unrelated is the minimum frequent 5 (33%). Conclusions: Thrombotic microangiopathy is a well-known complication of cyclosporine. Paying attention to signs of hemolysis and thrombocytopenia in the blood film are important clues in detecting early the diagnosis.