Офтальмологические изменения после сочетанной трансплантации почки и поджелудочной железы

Pancreas after kidney (PAK) transplantation is one of the accepted pancreas transplant modalities. We studied the impact of time interval between kidney and pancreas transplantation on the outcomes of PAK transplantation. Using OPTN/SRTR data, we included 1853 PAK transplants performed between 1996 and 2005 with follow-up until November 1, 2008. Kaplan-Meier survival and multivariate Cox regression analyses were performed using the time interval between kidney and pancreas transplantation either as a categorical (less than one yr, between one and less than three yr, and greater than or equal to three yr) or as a continuous variable (months) to assess kidney graft and patient survival. Patients who received a pancreas transplant three yr or later after kidney transplantation had higher risk of death-censored kidney graft loss (HR 1.56, 95% CI 1.04, 2.32, p = 0.03). Each month beyond three yr between kidney and pancreas transplantation incurred 1% higher risk of subsequent death-censored kidney graft loss (HR 1.01, 95% CI 1.001, 1.02, p = 0.03). In conclusion, time interval between pancreas and kidney transplantation is an independent risk factor of kidney graft loss following pancreas transplantation. Shortening the time interval between pancreas and kidney transplantation to less than three yr may reduce the risk of kidney graft loss in qualified PAK transplant candidates.

Immunosuppression: practice and trends

Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.

Pancreas transplant can have serious complications requiring salvage pancreatectomy, and surgical approaches should be carefully considered, with jejunal or ileal anastomoses most often employed. The jejunum may reduce gastrointestinal disturbance, whereas the ileum is more immunogenic. Proximal gastrointestinal anastomoses pose challenges with salvage pancreatectomy and creation of high-output stoma, often in the context of end-stage renal failure. Here, we compared outcomes between these techniques. We retrospectively analyzed patient records of simultaneous pancreas and kidney transplants at a single center between 2013 and 2015, with follow-up to 2020. Our center performed 86 simultaneous pancreas and kidney transplants during the study period; 10 patients were excluded because of incomplete records of anastomosis type. Of included recipients, 59.2% were men (mean age 41.5 ± 8.4 y), 72.4% were donors after brain death, and 98.7% had received a first pancreas transplant. Forty-three simultaneous pancreas and kidney transplants were performed with ileal anastomosis and 33 with jejunal anastomosis. We found no significant differences in recipient or donor factors or immunosuppression regimen between anastomosis groups and no significant differences in overall patient, pancreas, or kidney graft survival or in gastrointestinal complications. Hospital length of stay was higher with ileal anastomosis (median 14 vs 19 days; P < .05), as was cold ischemic time (median 8:48 vs 9:31 hours; P < .05). Three patients required salvage pancre-atectomy and loop ileostomy formation with multiorgan support, prolonged intensive care unit stay, relaparotomy, and/or laparostomy. Long-term outcomes were comparable between our patient groups. Catastrophic complica-tions occur in a minority of cases, requiring salvage surgery. More complications occurred with ileal anastomosis, but this approach allows graft pancreatectomy and formation of loop ileostomy, avoiding a more proximal stoma in clinically unstable patients. Further studies are needed to examine the impact of enteric anastomosis site.

Do we still need to demonstrate the survival benefit of pancreas transplantation?

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

Pancreas Transplant - Experience from Taipei Veterans General Hospital, Taiwan

Introduction: Simultaneous pancreas-kidney (SPK) transplantation is a treatment for patients with type1 diabetes (DM) and end-stage renal disease (ESRD). Complications of SPK transplantation include peripancreatic abscess, enterocutaneous fistula, and rarely, gastrointestinal bleeding (GIB). We report a case of an adult patient with SPK transplantation who presented with massive GIB caused by Meckel’s diverticulum. Case Report: A 40-year-old male presented 3 years after SPK transplantation to an outside hospital with maroon-colored stool and dizziness. His co-morbidities included DM, ESRD, coronary artery disease, hepatitis C, nonalcoholic steatohepatitis, and cirrhosis. He was hypotensive (94/43), but otherwise, vitals were within reference range. His exam was significant for a soft abdomen with normoactive bowel sounds and mild confusion without any focal deficits or asterixis. Labs were notable for a hemoglobin of 5.9 g/dL, creatinine 1.73 mg/dL (baseline 1.1 mg/dL), BUN 64 mg/dL, and liver function tests within reference range. An esophagogastroduodenoscopy (EGD) revealed presumed Dieulafoy’s lesion, which was cauterized and clipped. Colonoscopy showed mild inflammation, but no obvious source of bleeding. Biopsies were negative for infection or inflammatory bowel disease. The patient was transferred to our center for management of persistent GIB (requiring 26 units of blood total) and worsening renal function. At our center, EGD, colonoscopy, push enteroscopy, tagged RBC scan, and provocative angiography were negative for the source of bleeding. Video capsule endoscopy showed a large amount of red blood in the small bowel without adequate identification of the source lesion. Exploratory laparotomy with intraoperative small bowel endoscopy was performed, which demonstrated a healthy appearing anastomosis with a more distal Meckel’s diverticulum full of clotted blood. The diverticulum was excised without recurrent bleeding. Discussion: The differential for lower GIB is vast, but in adult patients, Meckel’s diverticulum is a rare cause. Patients status-post SPK transplantation have additional considerations for GIB, including anastomotic site ulcer, pseudoaneurysm, arterioenteric fistula, severe graft rejection, and cytomegalovirus infection. This is a rare case of GIB secondary to Meckel’s diverticulum in patients with SPK transplantation. Clinicians should be aware of Meckel’s diverticulum as a cause of massive GIB in SPK transplant patients. A high index of suspicion and timely evaluation can improve morbidity and mortality.

Renal pathology and clinical presentations of polyomavirus nephropathy in simultaneous kidney pancreas transplant recipients compared with kidney transplant recipients

A 46-year-old Black British man attended transplant follow-up. He had a history of Type 1 diabetes (T1D) diagnosed at the age of 14, with modest glucose control. He developed significant diabetic nephropathy progressing to severe chronic kidney disease and underwent pre-emptive simultaneous pancreas and kidney (SPK) transplantation 6 years previously. Transplant renal function was good and regular glycated haemoglobin tests were normal (36–41 mmol/mol [5.6%–5.9%]). At his most recent transplant clinic visit, his glycated haemoglobin had risen to 72 mmol/mol (8.7%). He was assessed urgently in the renal transplant diabetes clinic. His immunosuppression treatments were tacrolimus, mycophenolate mofetil and prednisolone 5 mg daily at stable doses over the preceding months. What are the potential reasons for hyperglycaemia following SPK transplantation? What investigations are required? He was asymptomatic, but home capillary blood glucose tests ranged from 5.6 mmol/L–13.6 mmol/L. Blood tests showed a normal serum lipase, a C-peptide of 899 pmol/L (paired glucose 7.9 mmol/L) and weakly positive glutamic acid decarboxylase antibodies at a titre of 21 units/L (normal <6). He was noted to have had a 25 kg weight gain following the transplant, with a current body mass index of 32.5 kg/m2. His case was discussed with the transplant surgical team who undertook an urgent pancreatic biopsy. This showed no evidence of rejection but did show evidence of recurrent T1D, with insulitis affecting many islets. The clinical impression was that his hyperglycaemia was likely due to a combination of recurrent autoimmunity, with resultant loss of insulin secretion, which was exacerbated by insulin resistance due to significant weight gain (plus the impact of immunosuppression). He was commenced on metformin, but was unable to tolerate it and subsequently commenced on dulaglutide. He achieved 7 kg weight loss, and glycated haemoglobin has remained around 46–47 mmol/mol (6.3%–6.4%). His C-peptide has remained around 1000 pmol/L. Hyperglycaemia following SPK transplantation is important and requires investigation. The most important cause is rejection.1 Weight gain following SPK transplantation, however, is common.2 Hyperglycaemia may, therefore, also occur due to insulin resistance, or the effect of immunosuppressants such as steroids and calcineurin inhibitors. Recurrent T1D in a transplanted pancreas is rare. In a Spanish case series of 81 participants with pancreas transplants, only two participants developed recurrent T1D.3 Rates of pancreas graft survival post-SPK transplant are currently quoted at 86% at 1 year and 53% at 10 years.4 Mitigating weight gain is an important aim post-SPK transplantation and may aid the longevity of the pancreas graft. If there are symptoms of hyperglycaemia or insulin deficiency post-SPK, prompt use of insulin pending investigations is advised to reduce the risk of hyperglycaemic emergency. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Long-Term Outcomes of Pancreas After Kidney Transplantation in Small Centers: Is It Justified?

BackgroundThis study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases.MethodsWe identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality.ResultsPatients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03–1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1–1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03–1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3–1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71–0.87).ConclusionsT2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.

Diabetes results in microvascular and macrovascular complications such as nephropathy, retinopathy and cardiovascular disease. Pancreas transplantation restores metabolic derangement and reduces or halts some of these complications therefore improves patient survival. Simultaneous pancreas and kidney transplant (SPK) is the most common approach while pancreas transplant after kidney transplant (PAK) is increasingly performed. We report our 15 years experience with 87 pancreas transplant procedures in 81 diabetic patients at the ALTRA Southern Alberta Transplant Program in Canada (73 SPK and 14 PAK, 3 patients received repeat pancreas transplant). The patient characteristics between these two groups are similar. Pre-emptive kidney transplantation is a major advantage of living kidney donation as all except one patient in PAK group had pre-transplant dialysis comparing to an average of 849 days of pre-transplant dialysis in SPK group. There is good patient survival in two groups after a median follow-up of 8.3 years (90.0±9.5% in PAK vs 83.2±5.3% in SPK). Excellent 10-year graft survival is achieved in both groups in kidney (85.7±13.2% in PAK vs 71.2±6.3% in SPK) and pancreas (61.2±14.0% in PAK vs 62.6±6.8% in SPK).Figure: No Caption available.Biopsy proven acute rejection rate was low and similar between SPK and PAK. In conclusion, both SPK and PAK transplantation lead to excellent long term patient and graft survival in type I diabetic patients. Pre-emptive kidney transplantation is a major advantage of living kidney donation followed by pancreas transplantation. DISCLOSURES:Tibbles, L.: Grant/Research Support, Pfizer.

OBJECTIVEDiabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients.RESEARCH DESIGN AND METHODSIn stage 1, we recruited 1,276 type 2 diabetic patients, including 378 patients with diabetic nephropathy but no retinopathy, 374 patients with diabetic retinopathy but no nephropathy, 244 patients with both diabetic retinopathy and nephropathy, and 280 control subjects with diabetes for >10 years and no diabetic retinopathy or nephropathy. Fifty-five SNPs from four loci (CPVL/CHN2, FRMD3, CARS, and IRS2) were genotyped. The SNPs that showed associations to diabetic retinopathy or nephropathy were genotyped in stage 2 samples for replication.RESULTSSNPs from CPVL/CHN2 and FRMD3 were associated with diabetic retinopathy with rs39059 and rs10868025 as the top SNPs (odds ratio [OR] 1.292, 95% CI 1.097–1.523, P = 0.0022, for rs39059; 1.201, 1.014–1.422, P = 0.0343, for rs10868025) in stage 1 samples. In stage 2 analysis, only rs39059 showed similar effect to diabetic retinopathy (OR 1.269, 0.989–1.628, P = 0.0689), and meta-analysis showed a significant association between rs39059 and diabetic retinopathy, with an OR of 1.285 (1.120–1.474, P = 0.0003). CPVL/CHN2 rs39059 was also associated with levels of diabetic retinopathy (P = 0.0007 for trend). However, no association was detected between these SNPs and diabetic nephropathy.CONCLUSIONSIn this study, we found CPVL/CHN2 rs39059 was associated with diabetic retinopathy in the Chinese type 2 diabetic patients.

Influence of Recipient Insurance on the Outcome of Simultaneous Pancreas and Kidney Transplantation.