Kidney Transplant in a Human Immunodeficiency Virus-Positive Patient: Case Report of Drug Interactions.

End-stage renal disease in the human immunodeficiency virus-positive population is increasing. Kidney transplant is the optimal therapy for this population rather than dialysis modalities if some criteria are met. These include undetectable plasma human immunodeficiency virus RNA, CD4 cell count over 200 cells/µL, and the absence of any AIDS-defining illness. Here, we describe the first living-donor kidney transplant in a human immunodeficiency virus-positive recipient in Turkey. The patient, a 52-year-old male diagnosed as human immunodeficiency virus positive, was on antiretroviral therapy, which consisted of 400 mg twice daily darunavir, 100 mg/day ritonavir, and 50 mg/day dolutegravir. He had been negative for human immunodeficiency virus RNA for the past 3 years. The patient developed renal insufficiency without any known cause and started hemodialysis. A living donor transplant from his son was performed, and the patient received ATG Fresenius-S (Neovii Biotech, Rapperswil, Switzerland) induction and a maintenance immunosuppression therapy consisting of methyl-prednisolone, mycophenolate mofetil, and tacrolimus. There were no incidences of delayed graft function or acute rejection. Because of tacrolimus and ritonavir interaction, tacrolimus trough levels were too high. With tacrolimus withdrawn, tacrolimus trough level decreased to detectable levels 2 weeks later. Antiretroviral therapy was continued on the same dosage. At month 4 posttransplant, the patient's creatinine level was 1.01 mg/dL. At present, the patient has had no complications and no episodes of rejection. Kidney transplant is the most favorable replacement therapy for HIV-positive patients who are under controlled AIDS care with highly active antiretroviral therapy. However, drug interactions should be carefully evaluated.

The effect of hypercalcemia on allograft calcification after kidney transplantation.

PURPOSE: Persistent hypercalcemia after kidney transplantation (KTx) may cause nephrocalcinosis and graft dysfunction. The aim of this study was to evaluate patients with hypercalcemia and assess its effect on tubulointerstitial calcification. METHODS: A total of 247 recipients were enrolled. Transient and persistent hypercalcemia was defined as hypercalcemia (corrected serum calcium >10.2 mg/dL) persisting for 6 and 12 months after KTx, respectively. The severity of calcification in the 0-h, 6- and 12-month protocol biopsies of patients with transient (n = 8) and persistent hypercalcemia (n = 20) was compared with a matched control group (n = 28). RESULTS: Twenty-eight patients were hypercalcemic at 6 months posttransplantation. Serum calcium levels were normalized in eight of them at the end of the first year. Dialysis duration was a positive predictor of persistent hypercalcemia. Tubulointerstitial calcification was detected in 70.6 and 90 % of patients with persistent hypercalcemia at 6 and 12 months posttransplantation, respectively. In 20 % of patients with transient hypercalcemia, severity of calcification regressed at 12 months posttransplantation along with normalization of serum calcium levels. Graft functions and histopathological findings (ci, ct, ci + ct, cv, ah, percentage of sclerotic glomeruli) were not different at 6 and 12 months posttransplantation. CONCLUSIONS: Hypercalcemia and persistent hyperparathyroidism are not rare after KTx. Tubulointerstitial calcification is more common and progressive among patients with persistent hypercalcemia. Normalization of calcium levels may contribute to regression of calcification in some patients.

A New Quantitative Index for Baseline Renal Transplant Scintigraphy With 99mTc-DTPA in Evaluation of Delayed Graft Function and Prediction of 1-Year Graft Function.

PURPOSE: The aims of this study were to assess quantitative indices of baseline renal transplant scintigraphy (RTS) with Tc-DTPA for evaluation of delayed graft function (DGF) and prediction of 1-year graft function and to describe a new inclusive index for RTS. PATIENTS AND METHODS: A total of 179 patients to whom RTS with Tc-DTPA was performed within 2 days after kidney transplantation were analyzed retrospectively. Hilson perfusion index, perfusion time (ΔP), peak-to-plateau ratio, peak perfusion-to-iliac artery ratio, T½ of graft washout, peak perfusion-to-uptake ratio, and ratio of uptake at 20 to 3 minutes (R20/3) were obtained. In addition, we first described the following formula defined as graft index (GI): GI = (ΔP × arterial peak × plateau)/(perfusion peak × uptake at 3 minutes). At 1 year, a serum creatinine level of more than 1.5 mg/dL was considered to be abnormal. Mann-Whitney U, Spearman coefficient of correlation test, and receiver operating characteristic curve were used for statistical analyses. P < 0.05 was considered statistically significant. RESULTS: Mean values of all the indices were significant. The most accurate, sensitive, and specific index for both identification of DGF and prediction of 1-year serum creatinine level of more than 1.5 mg/dL was GI. Area under the curve of GI was 0.94 for identification of DGF and 0.79 for 1-year prediction. CONCLUSIONS: The question is, "Which index is the best indicator?" This study demonstrated that the parameters of ΔP, plateau, arterial peak, perfusion peak, and uptake at 3 minutes of RTS could be assessed together by the formula of GI, which provides more accurate information to identify DGF and predict 1-year graft function.

The relationship between renal volume and histology in obese and nonobese kidney donors.

BACKGROUND: Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity-related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population. MATERIALS AND METHODS: Eighty-two kidney donors who underwent CT for the measurement of kidney volume and zero-hour renal biopsy for renal histology were included in this cross-sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h urine specimens as indicators of renal function. RESULTS: Mean body mass index (BMI) was 28 ± 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 ± 36 cm(3). RV was positively correlated with BMI, body surface area and creatinine clearance and negatively with HDL-cholesterol in the whole population. Renal function parameters of obese subjects were better, and their renal volumes were higher compared with the nonobese subjects. In obese subjects, corrected RV was positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected RV was significantly associated with chronicity index (OR: 0.96; P = 0.01). CONCLUSIONS: In obese cases, decreased RV determined by CT is associated with worse renal histology. In this population, kidney imaging techniques may provide important clues about renal survival.

Long-term outcome of kidney transplantation from elderly living and expanded criteria deceased donors.

The imbalance between organ demand and supply causes the increasing use of suboptimal donors. The aim of this study is to investigate the survival and allograft function of kidney transplantation from standard (SLD) and elderly living (ELD), standard criteria (SCDD) and expanded criteria deceased (ECDD) donors. All patients transplanted from 1997 to 2005 were investigated according to the donor characteristics. Data were collected retrospectively during the 83.4±43.1 months of follow-up period. ELD was defined as donor age≥60 years. ECDD was defined as UNOS criteria. A total of 458 patients were divided into four groups: SLD (n:191), ELD (n:67), SCDD (n:154), and ECDD (n:46). Seven-year death-censored graft survival in SLD, ELD, SCDD, and ECDD were 81.6%, 64.8%, 84.7%, and 68.3%, respectively (p=0.003). The death-censored graft survival in ELD group was lower than in SLD (p=0.007) and SCDD (p=0.007) groups, while in ECDD group it was lower than in SCDD group (p=0.026). Patient survival was similar. In ECDD group, 83% of total deaths occurred within the first 3 years, mainly due to infections (66.6%) (p<0.05). Estimated glomerular filtration rate (eGFR) was lower in ELD (compared with SLD and SCDD); and ECDD (compared with SCDD) at last visit. In multivariate analysis, ELD, experience of an acute rejection episode and presence of delayed graft function were the independent predictors for death censored graft loss. Transplantation of a suboptimal kidney provides inferior graft survival and function. A higher number of deaths due to infection in the early post-transplant period in the ECDD group are noteworthy.

Rare cause of weight loss in a kidney transplant recipient: iron overload.

Various reasons such as malignancies and chronic infections may cause weight loss in kidney transplant patients. In this report, iron overload as a rare cause of weight loss in a kidney transplant patient is presented. Forty-seven-year-old male patient who transplanted from a deceased donor 5 years ago was hospitalized because of 20 kg of weight loss. In medical history, he had history of hemodialysis for 89 months and received 100-300 mg of intravenous iron therapy per week before transplantation and transfused eight units of blood. In physical examination, weight and height were 45 kg and 185 cm, respectively. Respiratory and cardiac auscultation was normal. Laboratory results revealed as follow: glucose 76 mg/dL, urea 60 mg/dL, creatinine 1.35 mg/dL, aspartate aminotransferase 74 U/L, alanine aminotransferase 77 U/L, C-reactive protein 2.59 mg/dL, albumin 3.3 g/dL, globulin 3.4 g/dL, white blood cells 3200/mm(3), hemoglobin 13.1 g/dL and platelets 190,000/mm(3). Chest and abdominal tomography didn't reveal any pathology. Portal Doppler ultrasound showed signs of early cirrhosis. Viral and autoimmune hepatitis markers were negative. Ferritin was 5300 ng/mL and transferrin saturation was 82%. In liver biopsy, hemosiderosis was diagnosed and heterozygous H63D gene mutation was detected. Totally, 19 units of phlebotomy were performed. Liver function tests and serum ferritin decreased gradually. At outpatient follow-up in 6 months, he returned to former weight. In conclusion, there can be several causes of weight loss in kidney transplant patients. Iron overload can come across as a rare cause of weight loss. In these patients, ferritin levels should be checked and diagnosis should be clarified by liver biopsy and gene mutation analysis.

A rare cause of mechanical obstruction: Intestinal myeloid sarcoma.

Myeloid sarcoma is a rare aggressive tumour that originates from immature extramedullary myeloid cells. It can be seen as a relapse in patients with acute myeloid leukaemia. Sometimes it can be seen in the form of a solid tumour without any evidence of leukaemia. A case of a 44-year-old male patient who was admitted with symptoms and signs of mechanical intestinal bowel obstruction was operated on. The operation findings showed small bowel obstruction due to a mass. The mass was then resected with end-to-end intestinal anastomosis. The resected mass pathology results were consistent with myeloid sarcoma. The post-operative period was uneventful and adjuvant therapy was applied. In this case report we aimed to evaluate the clinical signs and treatment modalities of small intestinal myeloid sarcoma.

Multiple unrelated malignancies following renal transplantation: an evaluation of four cases.

The risk of de novo malignancy is significantly higher in patients who have undergone organ transplantation than in the general population. Long-term immunosuppressive treatment, in addition to age, genetic predisposition and infectious agents, plays a major role in the development of malignancy. Although skin and hemopoietic system cancers are common, atypical presentations of malignancies may occasionally be seen during long-term follow-up in patients with functioning allografts. In this report, four cases, each with more than one different primary malignancy (one patient with three malignancies and three patients with two malignancies), are presented.

A horseshoe kidney from a live donor as a renal transplant: case report.

OBJECTIVES: This case report presents our experience regarding a horseshoe kidney from live donor to be used as a renal transplant. MATERIALS AND METHODS: The recipient was a 48-year-old man with chronic renal failure owing to hypertension who had been on hemodialysis for 2 years. The donor was his 43-year-old sister who had an uncomplicated horseshoe kidney with negative results on a urinalysis. An aortogram showed that the arterial supply to the kidney consisted of 2 superior arteries (1 on each side) and 1 inferior accessory artery that was divided to feed the lower fused parenchyma of the kidney. RESULTS: Surgery was performed via a retroperitoneal lumbotomy incision; the left half of the kidney was mobilized. The left kidney was procured by clamping the inferior accessory renal artery, transecting the parenchyma within the demarcation boundary. The transplant kidney was placed in the recipient's contralateral iliac fossa. The graft vein was anastomosed to the recipient's external iliac vein, the artery to the external iliac artery, and the ureter to the bladder. After perfusing the graft, no urine leakage was detected from the transacted surfaces, and the graft began producing urine. There were no complications after surgery. The patient was discharged on the 10th day after surgery with a creatinine level of 0.07 µmol/L. Maintenance immunosuppressive treatment included tacrolimus, mycophenolate mofetil, and prednisolone. CONCLUSIONS: We believe using a horseshoe kidney as a renal allograft after a detailed preoperative evaluation may help expand the donor pool.

A mucormycosis case presented with orbital apex syndrome and hemiplegia in a renal transplant patient.

Solid organ transplantation is a risk factor for mucormycosis. Mucormycosis is a necrotizing opportunistic fungal infection with high morbidity and mortality. We report a fatal mucormycosis case with rhino-orbital-cerebral involvement in a renal transplant patient, which presented with orbital apex syndrome and hemiplegia.

Pre-transplant HbA1c level as an early marker for new-onset diabetes after renal transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a common complication in renal transplant (RT) patients. The clinical significance of pre-transplant HbA1c level remains unclear in RT patients. Thus, we investigated the predictive role of pre-transplant HbA1c levels for the NODAT diagnosed in 1 year after renal transplantation. METHODS: Two hundred and four RT patients older than 18 years were analyzed. NODAT diagnosis during the 1-year follow-up after RT was based on the 2003 modified criteria of the ADA. HbA1c level was measured at pre-transplantation period and every 3 months after RT. RESULTS: Mean age was 39.3 ± 10.7 (20-73) years and 36 % were female. Mean pre-transplant HbA1c level was 4.9 ± 0.5 % (4.0-6.4 %). Pre-transplant HbA1c level was positively correlated with age, pre-transplant body mass index (BMI) and cholesterol level. Fifty-four patients (25.9 %) developed NODAT and 33.8 % had impaired fasting blood glucose levels. Patients with NODAT were significantly older and had higher pre-transplant BMI and HbA1c than those without. Use of Tacrolimus was also higher in patients with NODAT. In stepwise logistic regression analysis, pre-transplant HbA1c level was an independent predictor for the development on NODAT (OR = 4.63, 95 % CI: 2.09-10.2, p < 0.001) together with age, Tacrolimus-based regimen and pre-transplant fasting blood glucose level. CONCLUSIONS: Assessment of pre-transplant HbA1c levels may be a valuable tool for early diagnosis of NODAT in RT recipients.

Aberrant breast in a rare site: a case report.

Aberrant breast tissue is an anomaly in the embryogenesis of the breast that is found along the mammary ridge or out of that line. We report a case of a 71-year-old female patient with an abdominal aberrant breast tissue found incidentally in a piece of mesenteric biopsy. The histological features were consistent with breast tissue.

Congenital adrenal hyperplasia: a rare cause of renal failure and a successful renal transplantation.

Congenital adrenal hyperplasia belongs to a group of autosomal recessive disorders affecting steroid biosynthesis; a rare disease with a prevalence of 1 case per 16,000 population. A 30-year-old phenotypically male patient had been diagnosed with 11-ß hydroxylase deficiency at the age of 16; presenting with ambiguous genitalia, growth retardation, presence of menstrual cycles, severe hypertension, hypokalemia and renal dysfunction. He developed endstage renal disease due to hypertension and was treated with hemodialysis for 3 y. After careful evaluation, he was approved to undergo renal transplantation. The patient has now finished 6th month after transplantation and is currently under follow-up at our outpatient clinic, having no problems related to the transplant. While early treatment to prevent hypertension is mandatory in patients with congenital adrenal hyperplasia, once renal failure occurs, renal transplantation may the best choice of treatment. In this study, we describe the first report of a successful renal transplantation in an adrenal hyperplasia.

Differential diagnosis of an unusual pelvic mass in a renal transplant recipient: multidrug-resistant abdominopelvic tuberculosis.

Renal transplant patients are more prone to tuberculosis infection due to the underlying intense immunosuppression, with an incidence 20-74 times higher than that in the general population. It is associated with graft dysfunction and increased mortality rates. It can be frequently pulmonary but extra-pulmonary involvement is not rare, and in the latter case, it may be misinterpreted as genital malignancies. In this case report, we discuss a renal transplant patient with pelvic pain and fever, who was later diagnosed as having abdominopelvic tuberculosis.

Nephrosclerosis and carotid atherosclerosis: lessons from kidney donor histology.

AIM: Carotid artery intima media thickness (CA-IMT) measurement has been shown to be a safe and reproducible method to assess severity of atherosclerosis. The association between nephrosclerosis and systemic atherosclerosis is not clear. In this study, we investigated the association between CA-IMT and nephrosclerosis in a group of kidney transplant donors. METHODS: Forty seven potential kidney transplant donors were included. CA-IMT was measured by B-Mode ultrasonography. Kidney allograft biopsy samples were obtained during the transplantation operation and chronic glomerular, vascular and tubulointertitial changes were semiquantitatively scored according to the Banff classification. RESULTS: Mean age was 52 ± 12 years and 55% of the cases were younger than 55 years. Mean CA-IMT was 0.74 ± 0.19 mm and 48% had IMT values > 0.75 mm. Chronicty index was ≥5 in 55% of the cases. Chronicity index was higher in cases older than 55 years. Age and CA-IMT were significantly correlated with chronic vascular changes and chronicity index. CA-IMT > 0.75 mm had a 46% sensitivity and 90% specificity to predict nephrosclerosis. Positive and negative predictive values were 85% and 57%, respectively. CONCLUSION: Aging leads to detrimental changes in every part of the vasculature of the human body. CA-IMT is correlated with the level of nephrosclerosis. Measurement of CA-IMT reflects nephrosclerosis especially in older patients.

Calcineurin inhibitor-based and free regimens have distinct gene expression patterns in subclinical graft fibrosis.

BACKGROUND: Chronic nephrotoxic effects of calcineurin inhibitors may be responsible for late allograft dysfunction and reduced allograft half-life. Mammalian target of rapamycin inhibitors (mTOR-i's), a newer class of immunosuppressant, do not have the chronic nephrotoxic effects shown with calcineurin inhibitors (CNI). Whether these drug classes have distinct features at the molecular level is not clear. MATERIAL/METHODS: Difference in gene expression profiles of kidney graft protocol biopsies from patients treated with CNI or mTOR-i's were investigated. Biopsies from patients using CNI (n=4) and mTOR-i-based treatments (n=4) were analyzed. The control group consisted of 5 biopsies obtained at the time of implantation (zero hour). Microarray hybridization was performed using the Affymetrix® GeneChip U133 plus 2.0 Array. RESULTS: In the CNI and mTOR-i groups, 64 up-regulated and 119 down-regulated genes were found compared to control subjects. A total of 29 genes in the CNI group and 101 genes in the mTOR-i group were up-regulated compared to each other. CONCLUSIONS: Despite similar clinical courses and histopathological appearances, different treatment strategies cause different gene expression profiles in kidney transplantation.

Progression of graft fibrosis under mammalian target of rapamycin inhibitor-based regimen.

AIM: Nephrotoxic potential of mammalian target of rapamycin inhibitors (mTORi) is different from calcineurin inhibitors (CNI). The aim of this study is to investigate the interstitial fibrosis (ci) and tubular atrophy (ct) progression from the baseline to first year under a mTORi-based, CNI-free regimen. METHODS: Thirty-five kidney transplant recipients who had to have adequate baseline and first year protocol biopsy were enrolled. Exclusion criteria were: the replacement of CNI at any time; acute deterioration in allograft functions; and serum creatinine level above 3 mg/dL at 12 months. Banff criteria were used for histopathological classification. Progression was defined as delta ci + ct ≥ 2 (difference between 12th month and baseline). RESULTS: Mean age of patients and donors were 34 ± 11 and 49 ± 10 years. Twelve patients had delayed graft function (DGF). The maintenance regimen consisted of sirolimus (n = 24) and everolimus (n = 11) with mycophenolate mofetil and steroids. Incidence of acute rejection was 25.7%. At baseline, the incidence of nil and mild fibrosis were 80% and 20%, respectively. At 12 months, 17.1% of patients had moderate, 40% had mild and 42.9% had nil fibrosis. Histological progression from baseline to first year was present in 34% of patients. In multivariate analysis the presence of DGF (P = 0.018) and deceased donor type (P = 0.011) were the most important predictors for fibrosis progression. CONCLUSION: Progression of graft fibrosis may be seen in one-third of patients under a mTORi-based regimen particularly manifested in deceased donor recipients with subsequent DGF.

Management of small bowel volvulus in a patient with simultaneous pancreas-kidney transplantation (SPKT): a case report.

There are several surgical complications which can occur following simultaneous pancreas-kidney transplantation (SPKT). Although intestinal obstruction is known to be a common complication after any type of abdominal surgery, the occurrence of small bowel volvulus, which is one of the rare causes of intestinal obstruction, following SPKT has not been published before. A 24-year-old woman suffering from type I diabetes mellitus with complications of nephropathy resulting in end stage renal disease (ESRD), neuropathy and retinopathy underwent SPKT. On the postoperative month 5, she was brought to the emergency service due to abdominal distention with mild abdominal pain. After laboratory research and diagnostic radiological tests had been carried out, she underwent exploratory laparotomy to determine the pathology for acute abdominal symptoms. Intra-operative observation revealed the presence of an almost totally ischemic small bowel which had occurred due to clockwise rotation of the mesentery. Initially, simple derotation was performed to avoid intestinal resection because of her risky condition, particularly for short bowel syndrome, and subsequent intestinal response was favorable. Thus, surgical treatment was successfully employed to solve the problem without any resection procedure. The patient's postoperative follow-up was uneventful and she was discharged from hospital on postoperative day 7. According to our clinical viewpoint, this study emphasizes that if there is even just a suspicion of acute abdominal problem in a patient with SPKT, surgical intervention should be promptly performed to avoid any irreversible result and to achieve a positive outcome.

Pediatric renal transplantation: single center experience.

Although renal transplantation (RTx) is actually the first choice of treatment for children with end-stage renal disease, the number of transplanted children remains low in comparison with adults. The experience of the individual pediatric transplant center is very important in the outcome of pediatric transplant recipients. In this study, our pediatric renal transplantation experience is presented. We retrospectively analyzed the results of 72 pediatric renal transplants performed at Ege University Pediatric Nephrology Transplantation Center between June 1989 and May 2003. They were 40 girls, 32 boys and their mean RTx age was 13.27+/-3.73 yr (range 3-20 yr). Thirty-eight (52.8%) of the transplanted kidneys came from a living related donor, and 34 (47.2%) from a cadaveric donor. Preemptive RTx was performed in one patient and a second RTx was performed in one patient after two-period hemodialysis. Hypertension (31.9%), acute rejection (27.8%) and chronic rejection (13.9%) were the most common complications. Cytomegalovirus (CMV) infection occurred in 15 children (20.8%), none of whom died or lost their graft as a result of the infection. Pretransplant acquired hepatitis C virus (HCV) infection was detected in 12 patients (16.7%). Urinary tract infections (UTIs) were seen in 31 (43.1%) recipients. The 1, 5 and 10 yr graft survival rates were 91, 84 and 77%, respectively, and corresponding patient survival rates were 97, 84 and 77%, respectively by Kaplan-Meier method. The graft and overall survival was not correlated with sex, donor type, treatment modality, acute rejection episodes, hypertension, UTIs, CMV and HCV infection.