Kunam S. Reddy

Impact of Subclinical Inflammation on the Development of Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients

Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1‐year protocol biopsy in patients on rapid steroid withdrawal (RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1‐year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1‐year biopsy (OR 6.62, 95% CI 2.68–16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW.

Relationship between Inpatient Hyperglycemia and Insulin Treatment after Kidney Transplantation and Future New Onset Diabetes Mellitus

BACKGROUND AND OBJECTIVES Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose > or = 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C > or = 6.5%, fasting venous serum glucose > or = 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. RESULTS The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). CONCLUSION Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.

Hyperglycemia during the Immediate Period after Kidney Transplantation

BACKGROUND AND OBJECTIVES Hyperglycemia and new-onset diabetes occurs frequently after kidney transplantation. The stress of surgery and exposure to immunosuppression medications have metabolic effects and can cause or worsen preexisting hyperglycemia. To our knowledge, hyperglycemia in the immediate posttransplantation period has not been studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective, observational study to characterize the prevalence and assess the pharmacologic management of hyperglycemia in kidney transplant recipients who underwent transplantation at our center between June 1999 and December 2006. Data were abstracted from electronic and pharmacy databases. RESULTS The study cohort included 424 patients (mean age 51 yr; 58% men; 25% with pretransplantation diabetes). All patients with and 87% without pretransplantation diabetes had evidence of hyperglycemia (bedside glucose >or=200 mg/dl or physician-instituted insulin therapy), whereas the prevalence of hypoglycemia was low (4.5%). Hyperglycemia was sustained throughout hospitalization. All patients with and 66% without pretransplantation diabetes required insulin at hospital discharge. Patients with pretransplantation diabetes were treated primarily with short-acting insulin during the first 24 h after transplantation but were transitioned to long-acting insulin as the hospital stay progressed. CONCLUSIONS Investigators have historically attempted to identify hyperglycemia after hospital discharge. Our data indicate that a substantial number of patients without pretransplantation diabetes develop hyperglycemia and require insulin during the hospital phase of their care immediately after kidney transplantation. Prospective studies are needed to delineate factors that contribute to development of new-onset diabetes after transplantation among patients with transient hyperglycemia.

Pretransplant risk score for new-onset diabetes after kidney transplantation

OBJECTIVE New-onset diabetes after kidney transplantation (NODAT) has adverse clinical and economic implications. A risk score for NODAT could help identify research subjects for intervention studies. RESEARCH DESIGN AND METHODS We conducted a single-center retrospective cohort study using pretransplant clinical and laboratory measurements to construct a risk score for NODAT. NODAT was defined by hemoglobin A1c (HbA1c) ≥6.5%, fasting serum glucose ≥126 mg/dL, or prescribed therapy for diabetes within 1 year posttransplant. Three multivariate logistic regression models were constructed: 1) standard model, with both continuous and discrete variables; 2) dichotomous model, with continuous variables dichotomized at clinically relevant cut points; and 3) summary score defined as the sum of the points accrued using the terms from the dichotomous model. RESULTS A total of 316 subjects had seven pretransplant variables with P < 0.10 in univariate logistic regression analyses (age, planned corticosteroid therapy posttransplant, prescription for gout medicine, BMI, fasting glucose and triglycerides, and family history of type 2 diabetes) that were selected for multivariate models. Areas under receiver operating curves for all three models were similar (0.72, 0.71, and 0.70). A simple risk score calculated as the sum of points from the seven variables performed as well as the other two models in identifying risk of NODAT. CONCLUSIONS A risk score computed from seven simple pretransplant variables can identify risk of NODAT.

Regional Variations in Peer Reviewed Liver Allocation Under the MELD System

The Model for End‐Stage Liver Disease (MELD) is used to assign priority for liver transplantation candidates. The Organ Procurement and Transplantation Network (OPTN) approved recognized exceptional diagnoses (REDs) for which MELD fails to accurately measure priority. Centers can request increased MELD points in cases not recognized by this policy (non‐REDs). Our aim was to compare regional practices to justify non‐RED requests for MELD adjustments. The UNOS/OPTN database was queried to extract all adult cases for which a non‐RED MELD adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by region and justification. Data for 29 510 listings were available. 26 947 had complete diagnosis information. There were 827 non‐RED requests of which 477 (57.7%) petitions were approved by the regional review boards (RRBs). The approval rate varied significantly among regions (range: 28–75%, p < 0.0001). The most common non‐REDs were complications of portal hypertension (48%). The percentage of patients listed with non‐REDs varied significantly among regions (0.7–8.3 %, p < 0.0001), as did the proportion of patients transplanted with non‐REDs (2.1–31.9%, p < 0.0001). Demographics did not differ among regions requesting non‐REDs.Widespread regional variations exist in the handling of requests for non‐REDs. These variations point to the need for reform to standard exception criteria.

Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury

Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin‐fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non‐AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p‐value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.

Utility of the Endovascular Stapler for Right-Sided Laparoscopic Donor Nephrectomy: A 7-Year Experience at Mayo Clinic

BACKGROUND Management of the renal vasculature during right laparoscopic donor nephrectomy (LDN) to maximize vessel length has been controversial. The endovascular gastrointestinal anastomosis (GIA) stapler has been used for renal vascular control for our donors since the inception of our LDN program. We evaluated and compared the outcomes of right and left LDNs using a single method for hilar control. STUDY DESIGN A retrospective review was performed of the first 400 LDNs and respective recipients at our institution. Patient demographics, perioperative variables, graft function, and complications were analyzed. RESULTS Four hundred LDNs were performed between 1999 and 2007. Forty-one were on the right. There were no statistically significant differences between the donor groups or their respective recipients. There were 4 (1%) stapler malfunctions, all occurring on the left side; 2 of these procedures were converted to open to obtain hemostasis. There were nearly equal rates of vascular complications, 4.9% and 4.7%, in the right and left groups, respectively. The overall immediate graft failure rate was 2.3%. Right and left recipient creatinine levels up to 24 months demonstrated no statistically significant differences. CONCLUSIONS We propose that the endovascular GIA stapler for left and right laparoscopic donor nephrectomy is safe for the donor. It standardizes the process, minimizes the need for additional maneuvers in securing the renal hilum, and produces similar outcomes for the recipient. The transplant team also plays an equally large role in favorable graft outcomes.

Living Donor Kidney Transplantation With Multiple Renal Arteries in the Laparoscopic Era

OBJECTIVES To compare the postoperative complications and survival metrics after multiple renal arteries (MRA) and single renal artery (SRA) laparoscopically procured living donor kidney transplantation (LLDKT). MRA are the most frequently encountered anatomic variation during kidney transplantation. The long-term outcomes of LLDKT with MRA are not well characterized. METHODS A retrospective review of our institutions LLDKT database was performed. All surgeries were performed at a single tertiary care academic center between June 1999 and September 2008. Patients were divided into 2 cohorts (MRA vs SRA), and analysis was limited to patients with at least 1-year follow-up. RESULTS Of 584 LLDKTs, 510 had at least 1-year follow-up (median: 36 months). A total of 393 grafts had an SRA, whereas 117 (23%) had MRA. When complications were stratified by the Clavien classification system, no differences were noted between groups (P = .5). Furthermore, rates of vascular (P = .2) and urological (P = .9) complications were similar between groups. There was, however, a higher incidence of slow graft function in the MRA group (P = .01), despite similar rates of delayed graft function (P = .9) and acute rejection (P = .4). Furthermore, allograft survival was similar between both groups with 76% of MRA and 81% of SRA grafts functioning at 5 years (P = .49). Patient overall survival was likewise similar between groups with 88% of MRA and 86% of SRA recipients surviving at 5 years (P = .76). CONCLUSIONS Despite a higher incidence slow graft function, MRA in LLDKT does not adversely affect long-term allograft and patient overall survival.

Laparoscopic distal pancreatectomy: Does splenic preservation affect outcomes?

Although the spleen is often routinely resected during both open and laparoscopic distal pancreatectomies, a splenectomy can increase the risk of postoperative and life-long infectious complications. Spleen-preserving laparoscopic pancreatectomies can technically be more difficult because of the delicate dissection of the splenic vessels. We performed a retrospective review of 34 laparoscopic pancreatectomies done at our institution. All procedures were done laparoscopically without hand assistance. Attempts were made in all patients to conserve the spleen, which was successful in 10 patients (29%). In the splenectomy group, 9 patients had 12 surgical complications (26%), which was statistically significant compared with the spleen-preserving group, in which there were no complications. This included 7 patients with a pancreatic leak (20%) and 3 with postoperative hemorrhage requiring reexploration (9%). Patients with spleen-preserving pancreatectomies had significantly less blood loss and shorter operative time compared with patients who underwent concomitant splenectomy. Splenic preservation should be attempted in all patients undergoing laparoscopic distal pancreatectomy unless there are overriding oncological or anatomic concerns.

Laparoscopic incisional hernia repair after liver transplantation

Incisional hernias occur in up to 17% of patients after liver transplantation. Laparoscopic ventral hernia repair is associated with fewer wound complications and a decreased incidence of recurrence when compared to open hernia repair in nontransplant patients. This is a retrospective review of 13 patients who underwent laparoscopic incisional hernia repair (LAP group) after liver transplantation compared to 14 patients who had open repairs (OP group; all but one with mesh). Primary immunosuppression in both groups at the time of transplantation was tacrolimus, but more patients in the LAP group were on sirolimus at the time of hernia, while more patients in the OP group were on prednisone at the time of hernia repair. All operations were completed with a laparoscopic approach; there were no conversions to open. Length of stay differed significantly between the 2 groups, with a mean of 5.4 days for the LAP group compared to 2.7 days in the OP group (0.0059). Complications occurred in 2 (15%) of the patients in the LAP group and 5 (36%) in the OP group. One patient in the LAP group required mesh removal to exclude causes of recurrent ascites, and 1 in the OP group for mesh infection. One (7.6%) of the patients in the LAP group developed a recurrence, compared to 29% (4) of the OP group (P =0.3259). In conclusion, laparoscopic incisional hernia repair is safe in patients after liver transplantation, with a low risk of infection or recurrence. Liver Transpl 13:1576–1581, 2007.