Citations

AbstractMultiple risk factors are important predictors in the development of diabetic nephropathy (DN). Once DN has developed, it progresses steadily to renal failure. To determine the rate of renal function decline and the parameters that influence the rate of decline, we retrospectively reviewed the charts of patients with DN who had undergone dialysis or kidney transplantation at the Mayo Clinic from 1983 to 1993. Forty patients were found to have two or more iothalamate clearance (IothmCl) measurements where a slope of renal function decline over time, expressed as mL/ min/month/1.73 m2, can be calculated. The parameters examined included age of onset and duration of diabetes (DM), age at initial presentation, insulin dosage, glycosylated hemoglobin level, proteinuria, blood pressure (BP), number of antihypertensive medications (HTM), use of ACE inhibitors, creatinine, and initial IothmCl. The mean overall decline of clearance was 1.36±1.1 mL/min/month, corrected. Univariate regression analysis showed that only systolic and mean BP (p<0.05), use of HTM (p=0.02), and the number of HTM used (p=0.0001) correlated with the rate of clearance decline. No other parameter was significant. The decline of IothmCl was 0.72±0.41, 1.20±0.9, and 2.34±1.38 mL/min/month, for patients taking no HTM, <3 HTM, and ≥ 3HTM, respectively. Of the eight patients on HTM who presented with initial IothmCl of <30 mL/min/1.73 m2, seven (88%) had clearance of <10 mL/min/1.73 m2 within 1 yr. We conclude that hypertension is an important marker of DN progression, and that the more HTM required for control of BP, the faster the decline of renal function. We recommend that a suitable transplant candidate with DN who presents with hypertension requiring HTM and a clearance of <30 mL/min should be placed on the transplant waiting list.

AbstractIntroductionCytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high‐risk recipients. However, delayed‐onset post‐prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post‐HSCT.MethodsRetrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event.ResultsAmong 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty‐six (15.7%) developed a breakthrough csCMVi. Delayed‐onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed‐onset csCMVi (OR 0.23).ConclusionsHaving a matched unrelated donor, a CMV donor negative/recipient positive status, and a non‐AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients. image

AbstractBackgroundIgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10–20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single‐center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile.MethodsA retrospective study was done of all renal transplant patients who had had biopsy‐proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed.Results53 renal allografts were transplanted to 51 biopsy‐proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA‐mismatched living related donor (LRD) kidneys, 29 one haplotype‐matched LRD and 9 HLA‐identical LRD organs. Five‐year actuarial graft survival was 100% in HLA‐ identical LRD, 88% in one haplotype‐matched LRD, and 74% in CAD grafts. All three HLA‐mismatched LRD kidneys were functioning up to 1.6 yr (longest follow‐up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allografts and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA‐matching in LRD transplantation.ConclusionRenal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.

We examined the value of thallium‐201 myocardial perfusion scintigraphy in noninvasive assessment of cardiac risk in 36 insulin‐dependent (type 1) diabetic patients being evaluated for pancreas or combined pancreas/kidney transplantation. An extensive cardiovascular evaluation including electrocardiogram was performed in all patients, and most patients were also evaluated by two‐dimensional and Doppler echocardiography. Exercise thallium studies were performed in 31 patients. Five patients were unable to exercise and underwent dipyridamole‐thallium study. The thallium images were abnormal in 12 patients, 10 of whom underwent coronary arteriography. Significant coronary artery disease was found in 7 of these patients. Nineteen patients underwent pancreatic (3 patients) or pancreato‐renal (16) transplantation without any occurrence of cardiac death or nonfatal myocardial infarction peri‐operatively or on follow‐up ranging from 7 months to 21 months. In contrast, 3 cardiac events occurred in 12 patients not approved for transplantation, each of whom had an abnormal thallium study exhibiting significant ischemia. Resting left ventricular global and regional function was not helpful in determining perioperative risk. Thus, thallium‐201 myocardial perfusion scintigraphy may be useful in identifying diabetic patients at low risk for pancreas transplantation and may obviate the need for routine coronary angiography in these patients.

Management of transplant renal artery stenosis has been a controversial issue. The authors have reviewed their experience with 31 such cases which represent 3.1% of a transplant population of 1015 patients. Evidence of chronic allograft rejection was noted in 14 of these patients. Ten patients were treated medically. The remaining patients were managed by either percutaneous transluminal angioplasty (8 cases) or surgery (13 cases). Three patients initially treated by percutaneous transluminal angioplasty later underwent surgical repair. Operative intervention resulted in a significant decrease in mean arterial pressure and the greatest degree of therapeutic success (defined as normal blood pressure without use of antihypertensive agents). In contrast to other reports, use of percutaneous transluminal angioplasty was not successful in a majority of patients. This divergence may reflect differences in criteria for success which, we believe, should be defined more rigorously. Our data indicate that decisions regarding definitive management strategies should be based on the specific characteristics of the lesion with identification of stenoses that may be amenable to surgical rather than angioplastic treatment.

Currently in pancreas transplantation, only indirect evidence of graft dysfunction is used as the mainstay of diagnosing a rejection episode. However, histologic specimens obtained by open surgical procedures are required for diagnostic dilemmas. After demonstrating the safety and efficacy of a cystoscopically‐directed biopsy technique to obtain adequate histologic specimens in a canine pancreaticoduodenal allograft model, we began using a similar technique in our human recipients. Between December 1987 and January 1989, 16 patients received a pancreaticoduodenal allograft with a duodenocystostomy at the Mayo Clinic. Cystoscopically‐directed needle biopsy specimens of the pancreas were obtained at the time of graft dysfunction (hypoamylasuria) and at 10 days after transplantation. The biopsy procedure consisted of obtaining pancreatic core tissue specimens with an 18‐gauge Menghini biopsy needle introduced through a rigid side‐viewing néphroscope that had been inserted transurethrally through the urinary bladder into the transplanted duodenal segment. The specimens were identified to be adequate histologically if acinar tissue was present. Each biopsy procedure was followed closely by clinical and ultrasonic examinations and serum amylase determinations. In 12 recipients, we performed 23 cystoscopically‐directed biopsies and 14 specimens (61%) were adequate. However, of our last 13 biopsy specimens, 12 (92%) were adequate. The follow‐up time per biopsy was an average of 103 d (range, 4 to 290 d). We had only two complications. Both were episodes of moderate hematuria that resolved with less than 24 hours of urinary catheter drainage. No fistulae, pseudocysts, hematomas, episodes of pancreatitis, or infections related to the biopsy procedure were documented. We have demonstrated that the cystoscopically‐directed biopsy technique is a safe procedure in human pancreaticoduodenal transplantation. This procedure can be used to differentiate the many causes of graft dysfunction.

Biliary tract complications are a significant risk following orthotopic liver transplantation (OLT). We reviewed the biliary tract complications of the first 50 liver transplants in 44 recipients performed in our institution. The mean follow‐up was 8 months (range 1 to 16 months). Biliary tract complications that required surgical or instrumental intervention developed in 17 of the 50 (34%) transplants. No deaths were attributable to biliary tract complications. Hepatic artery thrombosis caused the biliary tract complication in 3 transplants (1 stenosis, 2 anastomotic leaks) and a cystocele of the cystic duct remnant caused 1 common bile duct obstruction. The other 13 complications were associated either with the type of anastomosis performed or type of stent used. An end‐to‐end choledochocholedochostomy was performed in 31 transplants and 2 developed biliary tract complications (6.5%). One developed a biliary leak and the other developed a stenosis at the anastomosis. Nineteen of these choledochocholedochostomies were stented with a straight tube and 6 developed stent‐related complications. Twelve were stented with a T‐tube and only 1 stent complication occurred. An end‐to‐side choledochojejunostomy with a Roux‐en‐Y loop was performed in 19 patients. Only 1 early biliary complication occurred (5%), which was an anastomotic leak. However, 2 developed a stenosis of the entire donor extra‐hepatic duct, 12 and 13 months following transplantation. All anastomoses were stented with a straight tube and only 1 leak developed at the entrance site of the stent into the Roux‐Y. We conclude that the choledochocholedochostomy and the choledochojejunostomy with a Roux‐en‐Y loop are safe methods of biliary reconstruction following OLT. We recommend that a T‐tube be used for stenting the choledochocholedochostomy, and a hepatic artery thrombosis must be excluded when biliary tract complications develop.

Prostate cancer disproportionately affects Black men in the United States, leading to higher mortality rates and health disparities. In addition, based on historical mistreatment and discrimination and the resulting distrust of the medical system, Black populations are consistently underrepresented in health care-related research. Addressing these challenges requires community-driven approaches integrating diverse perspectives and fostering equitable health outcomes. This article describes the formation and impact of The Multidisciplinary Health Outcomes Research and Economics (MORE) Lab Community Advisory Board (CAB) at The University of Oklahoma Health Sciences. We purposefully recruited Black men with CaP and Black health care professionals to serve on a CAB and advise on ongoing research to address quality of life (QoL) issues in ethnically diverse Black CaP survivors. The CAB seeks to mitigate CaP disparities and improve health equity by empowering Black voices and promoting collaborative research practices. The MORE Lab CAB has successfully provided a venue for community members to contribute to designing a culturally relevant research program to improve the QoL in ethnically diverse Black men with CaP. The CAB has been instrumental in developing research goals and tools, implementing a series of town hall meetings to educate and support Black CaP survivors, and disseminating research findings. In conclusion, CABs are potentially critical in guiding research, enhancing community engagement, and advocating for culturally responsive health interventions.