Anaphylaxis secondary to citric acid allergy in End Stage Renal Disease patient.

Dialysis reactions are not uncommon in End Stage Renal Disease (ESRD) patients who are undergoing in-center hemodialysis. Here we report the first case of anaphylaxis related to citric acid solutions used for dialysis machine disinfection and descaling. The patient developed repeated episodes of anaphylactic reactions during hemodialysis only in the inpatient setting leading to respiratory failure needing intubation and anaphylactic shock. This had failed to resolve despite using various combinations of different dialysis machines and dialyzer membranes and only resolved after the elimination of citric acid from the dialysis circuit. This case highlights the importance of different allergens in dialysis circuits and emphasizes the importance of looking for alternative reasons for dialyzer reactions.

An incidental finding of large cell calcifying Sertoli cell tumor in an orchidectomy specimen for a separate adenomatoid tumor.

Introduction: Large cell calcifying Sertoli cell tumors are exceedingly rare. They are most commonly benign, but risks for malignancy include older age, larger size of tumor, and solitary tumors. To the author's knowledge, this is the first case reported of an incidental large cell calcifying Sertoli cell tumor when an orchidectomy was performed for a separate lesion. Case presentation: A 31-year-old male presented with a painless testicular lump. Ultrasound demonstrated an exophytic lesion in the superolateral aspect and calcifications were noted inferomedially and inferolaterally in the right testis. On histology from radical orchidectomy, the superolateral lesion was found to be an adenomatoid tumor, and the calcifications inferiorly represented a large cell calcifying Sertoli cell tumor. The background showed foci of germ cell neoplasia in situ but no evidence of invasive malignancy. Conclusion: Calcifications on ultrasound in isolation may represent large cell calcifying Sertoli Cell tumors.

Nutcracker syndrome, conservative approach: a case report.

The nutcracker phenomenon (NCP) refers to the compression of the left renal vein, most commonly between the aorta and the superior mesenteric artery (SMA). Nutcracker syndrome (NCS) should be limited to patients who present with the characteristic clinical signs and symptoms alongside diagnostic imaging of the anatomy associated with the syndrome. We report a case of NCS presenting with painless visible hematuria and left flank pain. Imaging showed a left renal vein stenosis at the origin of the SMA with collateralization. Diagnosis of NCP is made by a variety of imaging techniques; approaches to the treatment of NCS include conservative methods, open surgical, laparoscopic or endovascular techniques. Correlation with symptoms, laboratory results and excluding other causes continues to be important in the workup of NCS. Collaboration with the establishment of an International Consortium database will aid in the understanding of this rare disease.

Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis.

BACKGROUND AND OBJECTIVES: Residual native kidney function confers health benefits in patients on dialysis. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes. This study assessed whether lower plasma concentrations of uremic solutes were associated with residual kidney function in pediatric patients on peritoneal dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Samples were analyzed from 29 pediatric patients on peritoneal dialysis, including 13 without residual kidney function and ten with residual kidney function. Metabolomic analysis by untargeted mass spectrometry compared plasma solute levels in patients with and without residual kidney function. Dialytic and residual clearances of selected solutes were also measured by assays using chemical standards. RESULTS: Metabolomic analysis showed that plasma levels of 256 uremic solutes in patients with residual kidney function averaged 64% (interquartile range, 51%-81%) of the values in patients without residual kidney function who had similar total Kt/Vurea. The plasma levels were significantly lower for 59 of the 256 solutes in the patients with residual kidney function and significantly higher for none. Assays using chemical standards showed that residual kidney function provides a higher portion of the total clearance for nonurea solutes than it does for urea. CONCLUSIONS: Concentrations of many uremic solutes are lower in patients on peritoneal dialysis with residual kidney function than in those without residual kidney function receiving similar treatment as assessed by Kt/Vurea.

A risk calculator to inform the need for a prostate biopsy: a rapid access clinic cohort.

BACKGROUND: Prostate cancer (PCa) represents a significant healthcare problem. The critical clinical question is the need for a biopsy. Accurate risk stratification of patients before a biopsy can allow for individualised risk stratification thus improving clinical decision making. This study aims to build a risk calculator to inform the need for a prostate biopsy. METHODS: Using the clinical information of 4801 patients an Irish Prostate Cancer Risk Calculator (IPRC) for diagnosis of PCa and high grade (Gleason ≥7) was created using a binary regression model including age, digital rectal examination, family history of PCa, negative prior biopsy and Prostate-specific antigen (PSA) level as risk factors. The discrimination ability of the risk calculator is internally validated using cross validation to reduce overfitting, and its performance compared with PSA and the American risk calculator (PCPT), Prostate Biopsy Collaborative Group (PBCG) and European risk calculator (ERSPC) using various performance outcome summaries. In a subgroup of 2970 patients, prostate volume was included. Separate risk calculators including the prostate volume (IPRCv) for the diagnosis of PCa (and high-grade PCa) was created. RESULTS: IPRC area under the curve (AUC) for the prediction of PCa and high-grade PCa was 0.6741 (95% CI, 0.6591 to 0.6890) and 0.7214 (95% CI, 0.7018 to 0.7409) respectively. This significantly outperforms the predictive ability of cancer detection for PSA (0.5948), PCPT (0.6304), PBCG (0.6528) and ERSPC (0.6502) risk calculators; and also, for detecting high-grade cancer for PSA (0.6623) and PCPT (0.6804) but there was no significant improvement for PBCG (0.7185) and ERSPC (0.7140). The inclusion of prostate volume into the risk calculator significantly improved the AUC for cancer detection (AUC = 0.7298; 95% CI, 0.7119 to 0.7478), but not for high-grade cancer (AUC = 0.7256; 95% CI, 0.7017 to 0.7495). The risk calculator also demonstrated an increased net benefit on decision curve analysis. CONCLUSION: The risk calculator developed has advantages over prior risk stratification of prostate cancer patients before the biopsy. It will reduce the number of men requiring a biopsy and their exposure to its side effects. The interactive tools developed are beneficial to translate the risk calculator into practice and allows for clarity in the clinical recommendations.

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury.

BACKGROUND: Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI. METHODS: Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS that bind to plasma proteins. RESULTS: Fractional clearance values for PAG, HIPP, IS, and PCS were >1.0 in patients with AKI as well as controls, indicating that these solutes were still secreted by the tubules of the injured kidneys. Fractional clearance values were, however, significantly lower in patients with AKI than controls, indicating that kidney injury reduced tubular secretion more than glomerular filtration (AKI versus control: PAG, 2.1±0.7 versus 4.6±1.4, P<0.001; HIPP, 10±5 versus 15±7, P=0.02; IS, 10±6 versus 28±7, P<0.001; PCS, 3.3±1.8 versus 10±3, P<0.001). Free plasma levels rose out of proportion to total plasma levels for each of the bound solutes in AKI, so that calculating their fractional clearance in terms of their total plasma levels failed to reveal their impaired secretion. CONCLUSIONS: Tubular secretion of organic solutes can be reduced out of proportion to glomerular filtration in AKI. Impaired secretion of protein-bound solutes may be more reliably detected when clearances are expressed in terms of their free, unbound levels in the plasma.

Plasma pseudouridine levels reflect body size in children on hemodialysis.

BACKGROUND: Dialysis in children as well as adults is prescribed to achieve a target spKt/Vurea, where Vurea is the volume of distribution of urea. Waste solute production may however be more closely correlated with body surface area (BSA) than Vurea which rises in proportion with body weight. Plasma levels of waste solutes may thus be higher in smaller patients when targeting spKt/Vurea since they have higher BSA relative to body weight. This study measured levels of pseudouridine (PU), a novel marker solute whose production is closely proportional to BSA, to test whether prescription of dialysis to a target spKt/Vurea results in higher plasma levels of PU in smaller children. METHODS: PU and urea nitrogen (ureaN) were measured in plasma and dialysate at the midweek hemodialysis session in 20 pediatric patients, with BSA ranging from 0.65-1.87m2. Mathematical modeling was employed to estimate solute production rates and average plasma solute levels. RESULTS: The dialytic clearance (Kd) of PU was proportional to that of ureaN (average KdPU/KdUreaN 0.69 ± 0.13, r2 0.84, p < 0.001). Production of PU rose in proportion with BSA (r2 0.57, p < 0.001). The pretreatment plasma level of PU was significantly higher in smaller children (r2 0.20, p = 0.051) while the pretreatment level of ureaN did not vary with size. CONCLUSIONS: Prescribing dialysis based on urea kinetics may leave uremic solutes at higher levels in small children. Measurement of a solute produced proportional to BSA may provide a better index of dialysis adequacy than measurement of urea.

More Dialysis Has Not Proven Much Better.

Patients maintained on standard three times weekly hemodialysis have a high mortality rate and a limited quality of life. Some of this illness is due to systemic diseases that have caused kidney failure, and thus may be irreversible. But we presume that imperfect replacement of normal kidney function by dialysis contributes importantly. Patients on hemodialysis are subject to fluctuations in extracellular fluid volume and inorganic ion concentrations and their plasma levels of many organic waste solutes remain very high. It is thus natural to suppose that their health could be improved by increasing the intensity of dialysis treatment. But despite a great deal of work over the past 20 years, evidence that such improvement can be obtained is generally lacking. Specific benefits can indeed be achieved. Patients who cannot control their intradialytic weight gains or plasma phosphate levels with standard therapy can benefit from extending treatment time. But we cannot promise the average patient that longer or more frequent treatment will reduce mortality or improve the quality of life.

European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study.

OBJECTIVE: To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and two iterations of the European Randomised Study of Screening for Prostate Cancer (ERSPC) Risk Calculator, one of which incorporates prostate volume (ERSPC-RC) and the other of which incorporates prostate volume and the prostate health index (PHI) in a referral population (ERSPC-PHI). PATIENTS AND METHODS: The risk of prostate cancer (PCa) and significant PCa (Gleason score ≥7) in 2001 patients from six tertiary referral centres was calculated according to the PCPT-RC and ERSPC-RC formulae. The calculators' predictions were analysed using the area under the receiver-operating characteristic curve (AUC), calibration plots, Hosmer-Lemeshow test for goodness of fit and decision-curve analysis. In a subset of 222 patients for whom the PHI score was available, each patient's risk was calculated as per the ERSPC-RC and ERSPC-PHI risk calculators. RESULTS: The ERSPC-RC outperformed the PCPT-RC in the prediction of PCa, with an AUC of 0.71 compared with 0.64, and also outperformed the PCPT-RC in the prediction of significant PCa (P<0.001), with an AUC of 0.74 compared with 0.69. The ERSPC-RC was found to have improved calibration in this cohort and was associated with a greater net benefit on decision-curve analysis for both PCa and significant PCa. The performance of the ERSPC-RC was further improved through the addition of the PHI score in a subset of 222 patients. The AUCs of the ERSPC-PHI were 0.76 and 0.78 for PCa and significant PCa prediction, respectively, in comparison with AUC values of 0.72 in the prediction of both PCa and significant PCa for the ERSPC-RC (P = 0.12 and P = 0.04, respectively). The ERSPC-PHI risk calculator was well calibrated in this cohort and had an increase in net benefit over that of the ERSPC-RC. CONCLUSIONS: The performance of the risk calculators in the present cohort shows that the ERSPC-RC is a superior tool in the prediction of PCa; however the performance of the ERSPC-RC in this population does not yet warrant its use in clinical practice. The incorporation of the PHI score into the ERSPC-PHI risk calculator allowed each patient's risk to be more accurately quantified. Individual patient risk calculation using the ERSPC-PHI risk calculator can be undertaken in order to allow a systematic approach to patient risk stratification and to aid in the diagnosis of PCa.

Clinical and pathologic characteristics of hereditary apolipoprotein A-I amyloidosis in Ireland.

AIM: Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder characterized by progressive accumulation of amyloid fibrils in tissues, leading to renal and hepatic disease. We describe the clinical manifestations and pathologic features of kidney disease in three Irish families. METHODS: This observational study examines all known cases of chronic kidney disease due to hereditary apolipoprotein A-I amyloidosis in Ireland. Patients were identified by physician interview. In all of the affected individuals the disease was caused by the Gly26Arg heterozygous mutation. Immunohistochemistry confirmed that amyloid deposits were composed of apolipoprotein A-I fibrils. Family trees and clinical data were obtained via analysis of patient medical records. RESULTS: The vast majority of affected cases had demonstrable kidney disease, with variable liver disease. Renal disease most commonly manifested as slowly progressive renal impairment with mild proteinuria. In one kindred, a severe, debilitating peripheral neuropathy was common among affected family members. Histology demonstrated tubulointerstitial fibrosis with amyloid deposition in the medulla. There was very high penetrance within affected families. Of five patients who were transplanted, one transplant was lost after 5 years due to recurrent disease. One patient died from sepsis shortly after transplant. CONCLUSION: Hereditary apolipoprotein A-I amyloidosis is characterized by slowly progressive renal disease. Amyloid is deposited in the renal medulla highlighting the need to examine the medulla on renal biopsy. Overall, kidney transplantation conferred a survival advantage.

Recurrence of anti-neutrophil cytoplasmic antibody-associated vasculitis in appropriately immunosuppressed renal transplant patients: a discussion of two cases.

BACKGROUND: Granulomatosis with polyangiitis (GPA) (formerly known as Wegener's granulomatosis) is a multisystem autoimmune disease of unknown aetiology. Renal disease manifests as a crescentic glomerulonephritis, with varying degrees of renal failure. Ten percent of patients progress to end-stage kidney disease. Relapse of GPA in renal transplant patients is rare, with a rate of 0.09 relapses per patient per year. PATIENTS AND METHODS: We describe two cases of GPA relapse in immunosuppressed renal transplant patients. RESULTS: These patients presented with new-onset graft disfunction, having previously had an uncomplicated posttransplant course. Both patients were on appropriate doses of immunosuppressive agents at the time of relapse, with therapeutic target levels of tacrolimus. We describe the background history and management of both patients. CONCLUSION: The cases described inform us that although recurrence of anti-neutrophil cytoplasmic antibody vasculitis in transplant patients is rare, it should remain on our list of differential diagnoses in allograft disfunction.

Glomerular disease recurrence in second and subsequent kidney transplants.

INTRODUCTION: Primary glomerular diseases such as primary focal segmental glomerular sclerosis (FSGS), IgA Nephropathy and membrano-proliferative glomerulonephritis (MPGN) may recur in renal transplants, and can potentially lead to graft failure. The rate of recurrence in second and subsequent renal transplants, following failure of the first graft due to recurrence, is unclear. METHODS: A retrospective review of the Irish transplant database from 1982 to 2009 was performed. Patients were included for analysis if their first graft failed due to biopsy-confirmed recurrent glomerular disease (primary FSGS, IgA nephropathy or MPGN) and they underwent subsequent re-transplantation. RESULTS: 3,330 deceased and living renal transplants were performed during the time period in question. 33 patients had a deceased donor renal transplant following recurrence of primary FSGS, IgA nephropathy or MPGN causing first graft failure. Clinically significant disease recurrence was seen in 44% of re-transplants at 10 years. Median second graft survival in this group was 9.1 years. The median graft survival was 10.5 years for all other re-transplants performed in Ireland during the same time period. CONCLUSION: Clinically significant disease recurrence does not necessarily affect re-transplants following loss of the first graft to disease recurrence. Selected patients who experience first graft failure due to recurrent glomerular disease should not be precluded from receiving a second transplant.

Effect of perioperative blood transfusions on long term graft outcomes in renal transplant patients.

BACKGROUND: It is established that blood transfusions will promote sensitization to human leucocyte antigen (HLA) antigens, increase time spent waiting for transplantation and may lead to higher rates of rejection. Less is known about how perioperative blood transfusion influence patient and graft outcome. This study aims to establish if there is an association between perioperative blood transfusion and graft or patient survival. MATERIALS AND METHODS: This was a single center, national, retrospective cohort study. Data was collected on patients who received kidney transplants over a 14-year period (n = 2,013). The primary outcomes were graft survival and mortality in patients who received blood transfusions in the perioperative period compared to those who did not. RESULTS: Patients who received blood transfusions had lower hemoglobin levels, were more likely to be male, and had higher rates of delayed graft function compared to those who did not receive a transfusion. The one year graft survival of those transfused was 83% compared to 94% in those not transfused (p = < 0.0001). Adjustment for confounding showed that the receipt of a blood transfusion remained associated with increased graft loss. Hemoglobin levels prior to transfusion did not have an influence on graft outcome. CONCLUSION: Perioperative blood transfusion is associated with reduced long-term graft survival.

Arterio-venous fistula buttonhole cannulation technique: a retrospective analysis of infectious complications.

BACKGROUND: There are two main methods of accessing arterio-venous fistulas (AVFs); the 'buttonhole' and the 'rope-ladder' cannulation technique. Several small studies have hypothesized that the buttonhole technique is associated with increased rates of fistula-associated infection. This study addresses this hypothesis. METHODS: A retrospective review of all patients attending a large outpatient haemodialysis clinic was performed. Data were collected on the method of cannulation, infection rates, implicated microorganisms, complications of infection and time on haemodialysis. RESULTS: A total of 127 patients had received haemodialysis via an AVF: 53 via the rope-ladder technique and 74 via the buttonhole technique. Nine episodes of clinically significant bacteraemia were recorded in the buttonhole group. This equated to a rate of 0.073 bacteraemia events per 1000 AVF days. There were no episodes of bacteraemia in the rope-ladder group. Eight infections were due to methicillin-sensitive Staphylococcus aureus (MSSA); one was due to Staphylococcus epidermidis. Three patients with MSSA bacteraemia subsequently developed infective endocarditis. Five patients who developed bacteraemia events had been undergoing home haemodialysis. CONCLUSIONS: This study highlights the infectious complications associated with buttonhole cannulation techniques. All organisms isolated in our cohort were known skin colonizers. The reason for the increased rates of infection is unclear. Given this high rate of often life-threatening infection, we recommend regular audit of infection rates. We currently do not recommend this technique to our patients receiving haemodialysis.

Immediate re-transplantation following early kidney transplant thrombosis.

Allograft thrombosis is a devastating early complication of renal transplantation that ultimately leads to allograft loss. We report here on our experience of nine cases of immediate re-transplantation following early kidney transplant thrombosis at a single centre between January 1990 and June 2009. The mean age was 42.9 years at time of transplant. For seven patients, the allograft thrombosis was their first kidney transplant and seven of the nine cases had a deceased donor transplant. The initial transplants functioned for a mean of 1.67 days and the patients received a second allograft at a mean of 3.1 days after graft failure. All of the re-transplants worked immediately. Four allografts failed after a mean of 52.5 months (2-155 months). Two of these died with a functioning allograft, one failed owing to chronic allograft nephropathy and one owing to persistent acute cellular rejection. The remaining five patients still have a functioning allograft after a mean of 101.8 months (7-187 months). One year allograft and patient survival after re-transplantation were 87.5% and 100% respectively (after 5 years, both were 57%). Immediate re-transplantation following early kidney transplant thrombosis can be a success. It may be considered in selected cases after allograft thrombosis.

Cold intravascular organ perfusion for renal hypothermia during laparoscopic partial nephrectomy.

PURPOSE: We report initial data on the safety and functional outcomes of renal hypothermia with arterial cold perfusion during partial nephrectomy. MATERIALS AND METHODS: From June 2007 to June 2009, 31 consecutive patients underwent laparoscopic partial nephrectomy with hypothermia using renal arterial perfusion with cold, lactated Ringer's solution during renal ischemia. Doppler echography was done intraoperatively to evaluate renal perfusion. Complication data were reported prospectively. Median followup was 57 weeks (IQR 28, 83). RESULTS: The lowest recorded renal temperature during ischemia was 14C. Median tumor size was 4.0 cm (IQR 2.7, 6.2). Median estimated blood loss was 150 cc (IQR 100, 275). Median ischemia time was 35 minutes (IQR 26, 41). Doppler echography identified intrarenal arterial blood flow postoperatively in all cases. The median change in the estimated glomerular filtration rate from preoperatively to postoperative day 2 was 4 ml per minute (IQR -29, 19). Two months postoperative in 20 patients the median change was 3.5 ml per minute (IQR -6, 16.5). At last followup in 31 patients the overall change in the estimated glomerular filtration rate was -0.5 ml per minute (IQR -6, 6). Six complications developed in a total of 5 patients, of which 5 were grade 2 or less. One grade 3 postoperative hemorrhage from an arteriovenous fistula at the tumor resection site was treated with angiography and selective embolization. CONCLUSIONS: Cold intravascular perfusion during laparoscopic partial nephrectomy can achieve renal hypothermia below 15C. It is not associated with an immediate risk of renal vascular injury or thrombosis, as measured by Doppler echography in this series. Early changes in postoperative estimates of renal function appear minimal.