Recurrent 2,8‐Dihydroxyadenine Nephropathy: A Rare but Preventable Cause of Renal Allograft Failure

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8‐dihydroxyadenine (2,8‐DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8‐DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5–312) weeks following the transplant procedure. Patients had delayed graft function (n = 2), acute‐on‐chronic (n = 5) or acute (n = 1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8‐DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8‐DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n = 7), remained stable (n = 1) or worsened (n = 1). At last follow‐up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8‐DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.     

Tailoring the Endovascular Management of Transplant Renal Artery Stenosis

In this study we analyze the different types of endovascular interventions (EVIs) in de novo transplant renal artery stenosis (TRAS) and its anatomical subtypes to examine any variation in recovery of allograft function, blood pressure control, EVI patency and allograft survival with respect to EVI type (DES: drug‐eluting stent, BMS: bare‐metal stent, PTA: percutaneous transluminal angioplasty). Forty‐five patients underwent a total of 50 primary EVIs (DES: 18, BMS: 26, PTA: 6). Patients were stratified according to medical co‐morbidities, graft characteristics, biopsy results, clinical presentation and TRAS anatomic subtypes (anastomotic: 26, postanastomotic: 17, bend‐kink: 2). There was significant improvement in allograft function and mean arterial blood pressure (MAP) control across all interventions (pre‐EVI‐creatinine [CR]: 2.8 ± 1.4, post‐EVI‐Cr: 2.1 ± 0.7, p < 0.001; pre‐EVI‐MAP: 117 ± 16, post‐EVI‐MAP: 112 ± 17, p = 0.03) with no significant difference among EVI types. There was no significant difference in allograft survival with respect to EVI type. Patency was significantly higher in EVIs performed with DES and BMS compared to PTA (p = 0.001). In the postanastomotic TRAS subtype, patency rates were significantly higher in DES compared to BMS (p = 0.012) in vessels of comparable reference diameter (≤5 mm).     

Successful Renal Transplantation in Small Children With a Completely Thrombosed Inferior Vena Cava

In small children with end‐stage renal disease, an adult‐sized kidney transplant is the best option. However, in the face of a completely thrombosed inferior vena cava (IVC), such transplants can be challenging, given the difficulty of achieving adequate renal venous outflow and the risk of graft thrombosis. Using a new technique to anastomose the renal vein to the right hepatic vein/IVC junction, we successfully implanted an adult‐sized graft in two small children (9.8 and 14 kg) who had end‐stage renal disease and a completely thrombosed IVC. After mobilizing the right lobe of the liver and obtaining total vascular occlusion of the liver, we used a Fogarty catheter to dilate the retrohepatic IVC. In the right hepatic vein, we made a venotomy and extended it inferiorly onto the retrohepatic IVC. To that venotomy, we anastomosed the donor left renal vein, using continuous 7‐0 Prolene sutures. Both patients attained excellent renal allograft function: One had a serum creatinine level of 0.30 mg/dL at 6 mo after transplant, and the other had a level of 0.29 mg/dL at 1 year. In these two small children with completely thrombosed IVC, our technique for transplanting an adult‐sized kidney provided adequate venous outflow.     

Metastatic Renal Cell Carcinoma in a Renal Allograft: A Sustained Complete Remission After Stimulated Rejection

We report the case of a 40‐year‐old woman who recovered from a diffuse metastatic renal cell carcinoma that developed from a kidney allograft. She was successfully treated by the induction of tumor rejection. Immunosuppression was discontinued, and transplant nephrectomy was deliberately delayed based on the expectation that the tumor mass would trigger the alloimmune response, which was stimulated with pegylated interferon‐α‐2a. Three years later, the patient remained in complete remission. Despite this severe context, the present case shows that the poor prognosis of allograft metastatic renal cell carcinoma could be dramatically reversed by taking advantage of the donor tumor origin to actively induce a specific alloimmune rejection of the tumor.     

Urinary MicroRNA as Biomarker in Renal Transplantation

Urine represents a noninvasive source in which proteins and nucleic acids can be assessed. Such analytes may function as biomarkers to monitor kidney graft pathology at every desired frequency, thereby providing a time window to prevent graft damage by therapeutic intervention. Recently, several proteins have been measured in urine as markers of graft injury. However, the specificity is limited, and measuring urinary proteins generally lacks the potential to predict early kidney graft damage. Currently, urinary mRNA and microRNA are being investigated to evaluate the prognostic value of changes in gene expression during the initial stages of graft damage. At such time point, a change in treatment regimen and dosage is expected to have maximum potency to minimize future decline in graft function. Both mRNA and microRNAs have shown promising results in both detection and prediction of graft injury. An advantage of microRNAs compared to mRNA molecules is their stability, a characteristic that is beneficial when working with urine samples. In this review, we provide the current state of urinary biomarkers in renal transplantation, with a focus on urinary microRNA. In addition, we discuss the methods used to study urinary microRNA expression.     

Urologist-Acquired Renal Access for Percutaneous Renal Surgery

Objectives. In most endourology programs an interventional radiologist is employed to acquire renal access for percutaneous renal surgery. Over the last 13 years the senior endourologist at Oregon Health Sciences University has acquired access without employing a radiologist. We report our experience with urologist-acquired renal access for percutaneous renal surgery in 522 cases.Methods. We reviewed the records of all patients at our hospital who underwent percutaneous renal surgery between August 1983 and December 1996 with renal access being obtained in the operating room by a urologist.Results. Four hundred fifty-six patients underwent 522 procedures. Indications for percutaneous renal surgery were renal and proximal ureteral calculi (n = 516), retained ureteral stent (n = 3), and intrarenal collecting system tumor (n = 3). We were successful in gaining access to 513 of 522 kidneys (98.3%). Access was obtained via a subcostal approach in 344 procedures, over the 12th rib in 152 procedures, over the 11th rib in 15 procedures, and transabdominally in 2 procedures. Sixty-five patients (12.7%) required a second or multiple sites to facilitate complete removal of calculi. Our overall complication rate was 15.3%. Blood transfusion was required in 5.4% of the cases, ileus developed in 1.9%, pneumothorax in 1.1%, intraoperative hydrothorax in 1.1%, postoperative pleural effusion requiring aspiration in 0.9%, and septic shock in 0.9%. Our overall success rate for stone removal was 94.5%.Conclusions. In our experience, the urologist is able to safely and effectively obtain percutaneous access to the collecting system for percutaneous renal surgery as a one-stage procedure without the aid of interventional radiologists.     

Bilateral Renal Angiomyolipoma

Angiomyolipomas are frequent tumours of the kidneys. They are very important in the differential diagnosis of other kidney tumours; sometimes they can present a large size and manifest as an acute massive retroperitoneal haemorrhage. They generally should not be treated unless there are life-threatening problems. In this case report, we present an acute surgical condition due to rupture and haemorrhage of a giant angiomyolipoma. In addition, we review the literature on angiomyolipomas and their severe complications in order to help young surgeons who may be involved in such difficult and life-threatening cases as ours.     

Renal allograft immunosuppression

The long-term effects of different immunosuppressive drugs and regimens on renal allograft histology are virtually unknown. Therefore, in order to investigate the long-term effects of triple drug treatment versus different combinations of two immunosuppressive drugs on allograft histology, a prospective, randomized trial was performed. One group received triple therapy consisting of low-dose cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), and three groups received combinations of two drugs, i.e., Aza plus CyA, Aza plus MP, and CyA plus MP. At 2 years, there were no significant differences with regard to graft (80%) or patient (87%) survival, or to graft function between the four groups. After 2 years, a protocol core biopsy was taken of all 102 patients having a functioning graft. Of these patients, 61 (60%) were still following the original, randomized treatment protocol; in the remaining cases, changes had occurred in the original protocol and so these cases were considered drop-outs in this study. Histological specimens were examined blindly by two independent observers. Most of the 34 histological variables examined showed no changes. Diffuse fibrosis was most frequent in the CyA plus MP group (70%) and significantly more severe than in the triple therapy group. Mesangial matrix increase in glomeruli was significantly less common in the triple therapy group (8%) than in any one of the double drug combination groups (47%). Two other changes in glomeruli--Bowman capsular thickening and global glomerular sclerosis--were also less frequent in the triple therapy group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Individual and Regional Factors of Access to the Renal Transplant Waiting List in France in a Cohort of Dialyzed Patients

Several studies have investigated geographical variations in access to renal transplant waiting lists, but none has assessed the impact on these variations of factors at both the patient and geographic levels. The objective of our study was to identify medical and non‐medical factors at both these levels associated with these geographical variations in waiting‐list placement in France. We included all incident patients aged 18–80 years in 11 French regions who started dialysis between January 1, 2006, and December 31, 2008. Both a multilevel Cox model with shared frailty and a competing risks model were used for the analyses. At the patient level, old age, comorbidities, diabetic nephropathy, non‐autonomous first dialysis, and female gender were the major determinants of a lower probability of being waitlisted. At the regional level, the only factor associated with this probability was an increase in the number of patients on the waiting list from 2005 to 2009. This finding supports a slight but significant impact of a regional organ shortage on waitlisting practices. Our findings demonstrate that patients' age has a major impact on waitlisting practices, even for patients with no comorbidity or disability, whose survival would likely be improved by transplantation compared with dialysis.     

Renal allograft immunosuppression

A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidnery allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n=12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81%, 88%, 88%, and 88%, respecively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 mol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3.5–4.2 mg/kg per day and CyA concentrations were equal.     

Solid Renal Masses in Transplanted Allograft Kidneys: A Closer Look at the Epidemiology and Management

The objective of this review is to explore the available literature on solid renal masses (SRMs) in transplant allograft kidneys to better understand the epidemiology and management of these tumors. A literature review using PubMed was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) methodology. Fifty‐six relevant studies were identified from 1988 to 2015. A total of 174 SRMs in 163 patients were identified, with a mean tumor size of 2.75 cm (range 0.5–9.0 cm). Tumor histology was available for 164 (94.3%) tumors: clear cell renal cell carcinoma (RCC; 45.7%), papillary RCC (42.1%), chromophobe RCC (3%), and others (9.1%). Tumors were managed by partial nephrectomy (67.5%), radical nephrectomy (19.4%), percutaneous radiofrequency ablation (10.4%), and percutaneous cryoablation (2.4%). Of the 131 patients (80.3%) who underwent nephron‐sparing interventions, 10 (7.6%) returned to dialysis and eight (6.1%) developed tumor recurrence over a mean follow‐up of 2.85 years. Of the 110 patients (67.5%) who underwent partial nephrectomy, 3.6% developed a local recurrence during a mean follow‐up of 3.12 years. The current management of SRMs in allograft kidneys mirrors management in the nontransplant population, with notable findings including an increased rate of papillary RCC and similar recurrence rates after partial nephrectomy in the transplant population despite complex surgical anatomy.     

Laparoscopic Versus Open Renal Procurement for Pediatric Recipients of Living Donor Renal Transplantation

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.     

原位低温阻断肾血管肾实质切开取石术

目的探讨原位低温阻断肾血管肾实质切开取石术治疗复杂性肾结石的效果。方法2000年3月～2005年1月采用原位低温阻断肾血管肾实质切开取石术治疗肾内型肾盂复杂性肾结石患者22例,术中快速静脉滴注肌苷2.0g,静滴20%甘露醇250ml。根据术前影像检查结果及术中所见选择肾切口径路:13例充填于各盏的鹿角状结石,行肾背侧Brodt线肾实质肾盏切开取石;5例肾下盏肾盂鹿角状结石,行肾盂肾实质联合切开取石;4例结石过多者,于肾皮质最薄处另作放射状切口取石。结果肾血管阻断时间平均45(30～60)min;手术时间平均110(90～180)min;平均失血量150(80～400)ml。结石一次取净21例,1例残余结石,术后2个月带双J管行ESWL碎石排出。术后1～2月复查肾功能,术前有肾功能损害的8例,血清Cr平均110.2μmol/L,血清BUN平均8.0mmol/L,均明显改善,其余患者肾功能无损害,无严重术后并发症。18例随访6个月～3年无一例复发。结论原位低温阻断肾血管肾实质切开取石术治疗复杂性肾结石安全有效、出血少、结石残留率低。     

Renal function in patients with nephrolithiasis

PURPOSE: We describe kidney function, as measured by creatinine clearance in stone formers, and classified by type of stone formed and systemic etiologies of stone formation. MATERIALS AND METHODS: The mean of 3 pretreatment 24-hour creatinine clearance measurements in each of 1,856 stone formers and creatinine clearance in 153 normal individuals were used. Clearance was adjusted for patient sex, age and body weight using general linear modeling. RESULTS: As a group, all stone formers had decreased clearance adjusted for age, sex and body weight compared to that in normal individuals. Although clearance was particularly low in cystine and struvite stone formers, they were below normal in even common CaOx stone formers. CONCLUSIONS: As a rule, patients with kidney stones do not have normal kidney function. In clinical management all efforts must be made to minimize renal injury, balancing the risks of obstruction from stones against those of urological procedures.     

Addressing Morbid Obesity as a Barrier to Renal Transplantation With Laparoscopic Sleeve Gastrectomy

Morbid obesity is a barrier to renal transplantation and is inadequately addressed by medical therapy. We present results of a prospective evaluation of laparoscopic sleeve gastrectomy (LSG) for patients failing to achieve significant weight loss with medical therapy. Over a 25‐month period, 52 obese renal transplant candidates meeting NIH guidelines for metabolic surgery underwent LSG. Mean age was 50.0 ± 10.0 years with an average preoperative BMI of 43.0 ± 5.4 kg/m² (range 35.8–67.7 kg/m²). Follow‐up after LSG was 220 ± 152 days (range 26–733 days) with last BMI of 36.3 ± 5.3 kg/m² (range 29.2–49.8 kg/m²) with 29 (55.8%) patients achieving goal BMI of <35 kg/m² at 92 ± 92 days (range 13–420 days). The mean percentage of excess weight loss (%EWL) was 32.1 ± 17.6% (range 6.7–93.8%). A segmented regression model was used to compare medical therapy versus LSG. This revealed a statistically significant increase in the BMI reduction rate (0.3 kg/m²/month versus 1.1 kg/m²/month, p < 0.0001). Patients also experienced a 40.9% decrease in anti‐hypertensive medications (p < 0.001) and a 49.7% decrease in total daily insulin dose (p < 0.001). LSG is a safe and effective means for addressing obesity in kidney transplant candidates in the context of a multidisciplinary approach.