Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

Treatment of acute iliofemoral deep vein thrombosis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to compare the efficacy of three available treatments for acute iliofemoral deep vein thrombosis (DVT): systemic anticoagulation, surgical thrombectomy, and catheter-directed thrombolysis. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and Scopus) and sought additional references from experts. Eligible studies enrolled participants with acute iliofemoral DVT and measured the outcomes of interest. Reviewers working independently in duplicate extracted study characteristics, quality, and outcome data (death, pulmonary embolism, local complications, hemorrhagic complications, postthrombotic syndrome, pain, quality of life, and surrogate markers of venous function such as valve competence and patency). We pooled relative risks (RRs) from each study using the random effects model and estimated the 95% confidence intervals (CIs). Bayesian indirect comparison techniques were used to compare thrombectomy to catheter-directed thrombolysis. RESULTS: We found 15 unique studies that fulfilled eligibility criteria. When compared to systemic anticoagulation, thrombectomy was associated with a statistically significant reduction in the risk of developing postthrombotic syndrome (RR, 0.67; 95% CI, 0.52-0.87), venous reflux (RR, 0.68; 95% CI, 0.46-0.99), and a trend for reduction in the risk of venous obstruction (RR, 0.84; 95% CI, 0.60-1.19). When compared to systemic anticoagulation, pharmacologic catheter-directed thrombolysis was associated with statistically significant reduction in the risk of postthrombotic syndrome (RR, 0.19; 95% CI, 0.07-0.48), venous obstruction (RR, 0.38; 95% CI, 0.18-0.37), and a trend for reduction in the risk of venous reflux (RR, 0.39; 95% CI, 0.16-1.00). Overall, the quality of evidence was low; downgraded due to the observational nature of the majority of studies, lack of comparability of study cohorts at baseline, loss to follow-up, imprecision, and indirectness of outcomes (surrogacy). There were insufficient data to compare the outcomes of thrombectomy to catheter-directed thrombolysis. CONCLUSIONS: Low-quality evidence suggests that surgical thrombectomy decreases the incidence of postthrombotic syndrome and venous reflux. Catheter-directed pharmacologic thrombolysis decreases the incidence of postthrombotic syndrome and venous obstruction.

Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery.

INTRODUCTION: The RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for acute kidney injury (AKI) was recently modified by the Acute Kidney Injury Network (AKIN). The two definition systems differ in several aspects, and it is not clearly determined which has the better clinical accuracy. METHODS: In a retrospective observational study we investigated 4,836 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass from 2005 to 2007 at Mayo Clinic, Rochester, MN, USA. AKI was defined by RIFLE and AKIN criteria. RESULTS: Significantly more patients were diagnosed as AKI by AKIN (26.3%) than by RIFLE (18.9%) criteria (P < 0.0001). Both definitions showed excellent association to outcome variables with worse outcome by increased severity of AKI (P < 0.001, all variables). Mortality was increased with an odds ratio (OR) of 4.5 (95% CI 3.6 to 5.6) for one class increase by RIFLE and an OR of 5.3 (95% CI 4.3 to 6.6) for one stage increase by AKIN. The multivariate model showed lower predictive ability of RIFLE for mortality. Patients classified as AKI in one but not in the other definition set were predominantly staged in the lowest AKI severity class (9.6% of patients in AKIN stage 1, 2.3% of patients in RIFLE class R). Potential misclassification of AKI is higher in AKIN, which is related to moving the 48-hour diagnostic window applied in AKIN criteria only. The greatest disagreement between both definition sets could be detected in patients with initial postoperative decrease of serum creatinine. CONCLUSIONS: Modification of RIFLE by staging of all patients with acute renal replacement therapy (RRT) in the failure class F may improve predictive value. AKIN applied in patients undergoing cardiac surgery without correction of serum creatinine for fluid balance may lead to over-diagnosis of AKI (poor positive predictive value). Balancing limitations of both definition sets of AKI, we suggest application of the RIFLE criteria in patients undergoing cardiac surgery.

The dose of continuous renal replacement therapy for acute renal failure: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of the literature to summarize the best available evidence regarding the mortality and morbidity associated with differing dosing regimens of continuous renal replacement therapy (CRRT) for patients with acute renal failure (ARF) in an intensive care unit setting. PATIENTS AND METHODS: We searched for randomized controlled trials in electronic databases from January 1990 through November 2009. Eligible trials compared two or more dosing regimens of CRRT in patients with ARF. Two reviewers working independently determined trial eligibility and extracted descriptive, methodological, and outcome data. Random-effects meta-analysis was used to assess relative risks (RR) and weighted mean difference. The I(2)-statistic was used to assess heterogeneity of treatment effect across trials. RESULTS: Seven trials were eligible for meta-analysis. We found no reduction in mortality in patients who received higher doses of CRRT (RR 0.88, 95% CI 0.75-1.03, I(2) = 74%). There was no difference in the requirement of renal replacement therapy at the conclusion of the study period (RR 1.12, 95% CI 0.86-1.46, I(2) = 3%). The overall quality of evidence was downgraded because of imprecision and heterogeneity. CONCLUSION: Increased dosing of CRRT is not associated with a decrease in mortality of patients with ARF in an intensive care unit setting.

Timing of referral for vascular access placement: a systematic review.

OBJECTIVE: This review was conducted to determine the optimal timing for referring patients with end-stage renal disease to vascular surgery for access placement. METHODS: A systematic review of the electronic databases (MEDLINE, EMBASE, Current Contents, Cochrane CENTRAL and Web of Science) was conducted through March 2007. Randomized and observational studies were eligible if they compared an early referral cohort with a late referral cohort in terms of patient-important outcomes such as death, access-related sepsis, and hospitalization related to access complications. RESULTS: We found no studies that fulfilled eligibility criteria. CONCLUSION: At the present time, the optimal timing for referral to vascular surgery for vascular access placement is based on expert opinion and choices made by patients and physicians.

Autogenous versus prosthetic vascular access for hemodialysis: a systematic review and meta-analysis.

OBJECTIVES: The autogenous arteriovenous access for chronic hemodialysis is recommended over the prosthetic access because of its longer lifespan. However, more than half of the United States dialysis patients receive a prosthetic access. We conducted a systematic review to summarize the best available evidence comparing the two accesses types in terms of patient-important outcomes. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and SCOPUS) and included randomized controlled trials and controlled cohort studies. We pooled data for each outcome using a random effects model to estimate the relative risk (RR) and its associated 95% confidence interval (CI). We estimated inconsistency caused by true differences between studies using the I(2) statistic. RESULTS: Eighty-three studies, of which 80 were nonrandomized, met eligibility criteria. Compared with the prosthetic access, the autogenous access was associated with a significant reduction in the risk of death (RR, 0.76; 95% CI, 0.67-0.86; I(2) = 48%, 27 studies) and access infection (RR, 0.18; 95% CI, 0.11-0.31; I(2) = 93%, 43 studies), and a nonsignificant reduction in the risk of postoperative complications (hematoma, bleeding, pseudoaneurysm and steal syndrome, RR 0.73; 95% CI, 0.48-1.16; I(2) = 65%, 31 studies) and length of hospitalization (pooled weighted mean difference -3.8 days; 95% CI, -7.8 to 0.2; P = .06). The autogenous access also had better primary and secondary patency at 12 and 36 months. CONCLUSION: Low-quality evidence from inconsistent studies with limited protection against bias shows that autogenous access for chronic hemodialysis is superior to prosthetic access.

Surveillance of arteriovenous hemodialysis access: a systematic review and meta-analysis.

OBJECTIVES: Hemodialysis centers regularly survey arteriovenous (AV) accesses for signs of dysfunction. In this review, we synthesize the available evidence to determine to what extent proactive vascular access monitoring affects the incidence of AV access thrombosis and abandonment compared with clinical monitoring. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and SCOPUS) and sought references from experts, bibliographies of included trials, and articles that cited included studies. Two reviewers independently assessed trial quality and extracted data. We used random effects meta-analysis to estimate the pooled relative risk (RR) and 95% confidence interval (CI) across studies and conducted subgroup analyses to explain heterogeneity. The I(2) statistic was used to assess heterogeneity of treatment effect among trials. RESULTS: Nine studies (1363 patients) compared a strategy of surveillance vs clinical monitoring. A vascular intervention to maintain or restore patency was provided to both groups if needed. Surveillance followed by intervention led to a nonsignificant reduction of the risk of access thrombosis (RR, 0.82; 95% CI, 0.58-1.16; I(2) = 37%) and access abandonment (RR, 0.80; 95% CI, 0.51-1.25; I(2) = 60%). Three studies (207 patients) compared the effect of vascular interventions vs observation in patients with abnormal surveillance result. Vascular interventions after an abnormal AV access surveillance led to a significant reduction of the risk of access thrombosis (RR, 0.53; 95% CI, 0.36-0.76) and a nonsignificant reduction of the risk of access abandonment (RR, 0.76; 95% CI, 0.43-1.37). CONCLUSION: Very low quality evidence yielding imprecise results suggests a potentially beneficial effect of AV access surveillance followed by interventions to restore patency. This inference, however, is weak and will require randomized trials of AV access surveillance vs clinical monitoring for rejection or confirmation.

Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

BACKGROUND: Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. OBJECTIVES: This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. METHODS: We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). RESULTS: Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). CONCLUSIONS: SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.

Outcome of untreated grade II rejection on solitary pancreas allograft biopsy specimens.

BACKGROUND: The most widely used grading scheme for acute pancreas allograft rejection grades biopsy specimens from 0 (normal) to V (severe rejection). Although the more advanced grades correlate strongly with immunologic graft loss, it is unclear how lesser grades impact graft outcome. The authors therefore report the outcomes of untreated grade II (minimal) rejection of solitary pancreas biopsy specimens. METHODS: The authors retrospectively analyzed all solitary pancreas transplants performed at the Mayo Clinic between January 2001 and November 2002. The authors selected all patients who were found with grade II findings on biopsy. Whether patients underwent follow-up biopsies, what the results were, and graft survival at the end of the study period were then determined. RESULTS: A total of 88 pancreas transplants were performed; 20 pancreas transplant recipients (23%) developed grade II (minimal) rejection and were followed for a mean of 22.8+/-8.7 months. Eighteen patients underwent biopsy for protocol purposes and two patients underwent clinically indicated biopsies. Of the patients who underwent biopsy as per protocol, 15 of the patients had a total of 25 follow-up biopsies: 10 were grade 0; 3 were grade I; and 10 were unchanged (grade II). Rejection in one patient progressed to grade III and in another patient to grade IV. The three patients who did not undergo repeat biopsy had a functioning allograft pancreas at the end of the study period. Of the two patients with grade II biopsy specimens obtained for clinical reasons, one had resolution of all inflammation noted on three follow-up biopsies, and the other patient did not undergo follow-up biopsy and died with a functioning graft. CONCLUSIONS: Grade II (minimal) rejection of solitary pancreas allograft rarely progresses to more severe degrees of inflammation. Morphologic findings in this category may not have unfavorable prognoses over a period of 2 years when untreated.

Seronegative anti-GBM Disease with Coexistent ANCA Positivity.

Anti-glomerular basement membrane disease has been reported to coexist with anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis. Seronegative anti-GBM disease has been previously described and mostly blamed for the relative insensitivity of earlier serologic assays. A 58-year-old male was transferred to our facility for acute kidney injury. Prior to his hospital admission, the patient had a 2 week history of progressive fatigue, fevers, anorexia, vomiting, decreased urine output, sinus congestion, and non-productive cough. His creatinine reached 13 mg/dL. P-ANCA was positive, anti GBM antibody was negative twice, and urinalysis showed hematuria. Chest x-ray demonstrated diffuse opacities, concerning for pulmonary hemorrhage. Renal biopsy showed a severe necrotizing and crescentic glomerulonephritis with circumferential crescents. There was bright linear glomerular basement membrane staining with IgG consistent with anti-GBM disease. Given these findings, the patient was started on oral cyclophosphamide (160 mg daily), in addition to pulse dose methylprednisolone. He was also initiated on therapeutic plasma exchange. Due to worsening renal function, hemodialysis was started. The patient was discharged from the hospital and completed a course of treatment with cyclophosphamide and prednisone but remains oligo-anuric and hemodialysis dependent at 150 days since presentation. This case highlights the importance of tissue diagnosis in situations similar to this.

Assessing the efficacy of kidney paired donation--performance of an integrated three-site program.

BACKGROUND: Kidney paired donation (KPD) has emerged as a viable option for renal transplant candidates with incompatible living donors. The aim of this study was to assess the "performance" of a three-site KPD program that allowed screening of multiple donors per recipient. METHODS: We reviewed retrospectively the activity of our KPD program involving three centers under the same institutional umbrella. The primary goal was to achieve a transplant that was both ABO compatible and had a negative or low-positive flow cytometric crossmatch (+XM). RESULTS: During the 40-month study period, 114 kidney transplant candidates were enrolled-57% resulting from a +XM and 39% resulting from ABO incompatible (ABOi) donors. Important outcomes were as follows: (1) 81 (71%) candidates received a transplant and 33 (29%) were still waiting; (2) 368 donors were evaluated, including 10 nondirected donors; (3) 82% (37/45) of ABOi candidates underwent transplantation; (4) 56% (36/65) of +XM candidates underwent transplantation (however, all but four of these had a cPRA less than 95%); (5) at the end of the study period, 97% (28/29) of +XM candidates still waiting had a cPRA greater than 95%. CONCLUSIONS: These data suggest evaluating large numbers of donors increases the chances of KPD. Patients with a cPRA greater than 95% are unlikely to receive a negative or low-positive +XM, suggesting the need for desensitization protocols in KPD.

Desensitization in the era of kidney paired donation: the Mayo Foundation 3-site experience.

Sensitized renal allograft candidates face significant barriers to transplantation. While several options exist, including: kidney paired donation (KPD), desensitization, or pursuing a deceased donor kidney transplant, it is unclear from existing data what is the appropriate protocol for an individual patient. In this study, we seek to devise a balance between waiting for a paired donor and combining desensitization with KPD.

Risk factors for development of acute kidney injury in critically ill patients: a systematic review and meta-analysis of observational studies.

Background. Acute kidney injury (AKI) is a frequent complication of critically ill patients. The impact of different risk factors associated with this entity in the ICU setting is unknown. Objectives. The purpose of this research was to assess the risk factors associated with the development of AKI in critically ill patients by meta-analyses of observational studies. Data Extraction. Two reviewers independently and in duplicate used a standardized form to collect data from published reports. Authors were contacted for missing data. The Newcastle-Ottawa scale assessed study quality. Data Synthesis. Data from 31 diverse studies that enrolled 504,535 critically ill individuals from a wide variety of ICUs were included. Separate random-effects meta-analyses demonstrated a significantly increased risk of AKI with older age, diabetes, hypertension, higher baseline creatinine, heart failure, sepsis/systemic inflammatory response syndrome, use of nephrotoxic drugs, higher severity of disease scores, use of vasopressors/inotropes, high risk surgery, emergency surgery, use of intra-aortic balloon pump, and longer time in cardiopulmonary bypass pump. Conclusion. The best available evidence suggests an association of AKI with 13 different risk factors in subjects admitted to the ICU. Predictive models for identification of high risk individuals for developing AKI in all types of ICU are required.