Improvement in diabetic neuropathy 4 years after successful pancreatic and renal transplantation

We have studied the fate of diabetic neuropathy and autonomic function in 13 patients with long standing Type 1 (insulin-dependent) diabetes mellitus following combined pancreas and kidney transplantation. Fifteen diabetic patients with a kidney graft only served as controls. After initial improvement of the neuropathy in both groups, probably caused by the elimination of uraemia, a continuous improvement during the 48 months study was seen in the euglycaemic pancreas graft recipients only. Autonomic (parasym-pathetic) function improved only slightly and to a similar extent in both groups.     

Neurophysiological study of the effect of combined kidney and pancreas transplantation on diabetic neuropathy: a 2-year follow-up evaluation

Previous study have reported a significant improvement of peripheral neuropathy following combined pancreas and kidney transplantation attributed to improvement of blood glucose control by some authors and to elimination of uraemia by others. To asses the specific role of uraemia and hyperglycaemia in neuropathy, 16 diabetic uraemic patients with combined pancreas and kidney transplantation were compared to 9 diabetic patients with a renal graft only. Neurophysiological studies of peripheral neuropathy included ulnar and deep peroneal nerve motor conduction velocity, median and sural nerve sensory conduction velocity were performed at baseline and 1 and 2 years after transplantation. One year after transplantation mean nerve conduction velocity significantly improved in both groups. However, changes were statistically significant in the kidney-pancreas group only. At the 2 year follow-up nerve conduction velocity had increased further in the pancreas-kidney group only. These data suggest that improvement of nerve conduction velocity following pancreas and kidney transplantation is predominantly due to the long-term euglycaemic state.     

Long-term outcomes after organ transplantation in diabetic end-stage renal disease

Patients with type 1 diabetic end-stage renal disease (ESRD) may be offered single kidney transplantation from a live donor (LDK) or a deceased donor (DDK) to replace the lost kidney function. In the latter setting the patient may also receive a simultaneous pancreas together with a kidney from the same donor (SPK). Also in some cases a pancreas after kidney may be offered to those who have previously received a kidney alone (PAK). The obvious benefit of a successful SPK transplantation is that the patients not only recover from uremia but also obtain normal blood glucose control without use of insulin or other hypoglycemic agents. Accordingly, this combined procedure has become an established treatment for type 1 diabetic patients with ESRD. Adequate long-term blood glucose control may theoretically lead to reduced progression or even reversal of microvascular complications. Another potential beneficial effect may be improvement of patient and kidney graft survival. Development of diabetic complications usually takes a decade to develop and accordingly any potential benefits of a pancreas transplant will not easily be disclosed during the first decade after transplantation. The purpose of the review is to assess the present literature of outcomes after kidney transplantation in patients with diabetic ESRD, with our without a concomitant pancreas transplantation. The points of interest given in this review are microvascular complications, graft outcomes, cardiovascular outcomes and mortality.     

Mono-oligoclonal immunoglobulin abnormalities in diabetic patients after kidney transplantation: influence of simultaneous pancreas graft

Summary Monoclonal components (MC) are detected in as high as 30 % of renal transplant recipients. Our aim was to evaluate the incidence, relevance and consequence of monoclonal components in patients with Type I (insulin-dependent) diabetes who received kidney (n = 22), kidney and whole pancreas (n = 41), kidney and segmental pancreas (n = 24) and kidney and islets (n = 12) transplants. Immunosuppression was based on prophylactic anti-lymphocyte globulins, corticosteroids, azathioprine and cyclosporin in all patients; acute rejection was treated with steroids or anti-lymphocyte monoclonal immunoglobulin therapy (OKT3) or both. Serum immunofixation was carried out in all patients before transplantation and then after at 6 months and then yearly. Monoclonal components were detected in 81 of 99 patients (82 %); 52 patients (52 %) developed them within 6 months of transplantation, 15 (15 %) between 6 and 12 months, with a peak prevalence at 1 year post-transplant (58 %) and a decrease thereafter (10 % at 9 years). Kidney recipients showed a lower incidence of monoclonal components when compared with those who received kidneys and segmental pancreases and those who received kidneys and whole pancreases. Monoclonal components were more often detected in patients who had previously experienced an acute renal rejection. Cytomegalovirus infection and acute rejection occurring in the same patient further increased the risk of developing monoclonal components, the development of which did not correlate with OKT3 treatment. A Post-transplant lymphoproliferative disorder was developed by two patients (2 %), one with 5 and the other with 6 monoclonal components. In conclusion, diabetic patients receiving kidney and/or Pancreas transplantation, experiencing both cytomegalovirus infection and acute rejection, are at greatest risk of developing monoclonal components but they appear to be benign and transient; multiple band detection is a marker for the subsequent development of post-transplant lymphoprolifertive disorder. [Diabetologia (1998) 41: 1176–1179] Received: 5 January 1998 and in revised form: 28 April 1998     

Corneal confocal microscopy: Recent progress in the evaluation of diabetic neuropathy

The present brief review discusses recent progress with corneal confocal microscopy for the evaluation of diabetic sensorimotor polyneuropathy. Corneal confocal microscopy is a new, non‐invasive and reproducible diagnostic modality, and it can also be easily applied for patient follow up. It enables new perspectives of studying the natural history of diabetic sensorimotor polyneuropathy, severity of nerve fiber pathology and documenting early nerve fiber regeneration after therapeutic intervention. It shows moderate to high sensitivity and specificity for the timely diagnosis of diabetic sensorimotor polyneuropathy. Currently, corneal confocal microscopy is mainly used in specialized centers, but deserves more widespread application for the assessment of diabetic sensorimotor polyneuropathy. Finally, further progress is required in terms of technical improvements for automated nerve fiber quantification and for analysis of larger images.     

High incidence of carpal tunnel syndrome in diabetic patients after combined pancreas and kidney transplantation

Fifty-eight patients with long-standing type 1 (insulin-dependent) diabetes were studied prospectively after combined pancreas and kidney transplantation for a mean observation period of 47.9 months (range 17–116 months). Thirty-three per cent of these patients (19/58) developed carpal tunnel syndrome after a mean interval of 1.7 years (range 3 months–5 years). This rate is about twice that in type 1 diabetic patients. The manifestation of carpal tunnel syndrome was not significantly associated with worsening of diabetic polyneuropathy or with deterioration of kidney or pancreas function. In all but one patient symptoms improved without surgical intervention. This study suggests that patients after combined pancreas and kidney transplantation have an increased risk of carpal tunnel syndrome for which the etiology and pathophysiology are unknown. In most patients no surgical intervention is necessary.     

Ophthalmological follow-up of Type 1 (insulin-dependent) diabetic patients after kidney and pancreas transplantation

We studied the effect of successful kidney and pancreas transplantation on visual function and diabetic retinopathy in 18 patients with long-term Type 1 (insulin-dependent) diabetes mellitus (17 to 38 years) and with advanced proliferative retinopathy. The average age of the patients was 42 years. Prior to transplantation, 5 eyes were in end-stage ophthalmic complication due to neovascular glaucoma. An ophthalmological follow-up was performed between 1–6 years post-surgery. Analysis of the results showed that the diabetic retinopathy had stabilized after transplantation in 12 cases (66 %) with a supplementary photocoagulation in the majority of cases. The proliferation continued in 4 patients (22 %) leading to blindness in 2 patients and recurrence of vitreous haemorrhages despite the photocoagulation in the other 2 cases. An improvement was observed on fluorescein angiography in a patient with pre-papillar glial proliferation without photocoagulation. Ten patients were reported to have a cataract and were operated on in two cases before transplantation; in one patient, the cataract increased following transplantation. In conclusion, the kidney and pancreas transplantation was not effective in our patients in reversing the clinical and angiographic signs of diabetic retinopathy. Moreover, a worsening of the lesions was observed in some cases; this was probably due to the irreversible microangiopathic lesions due to advanced evolution of diabetes.     

Skin microvascular reactivity in fingers of diabetic patients after combined kidney and pancreas transplantation

Nine patients with severe late diabetic complications were investigated 2 and 38 months after successful combined kidney and pancreas transplantation. Nine healthy subjects served as controls. Blood cell velocity in single capillaries was evaluated by videophotometric capillaroscopy, and total skin microcirculation of the same area by laser Doppler fluxmetry. The measurements were performed during rest, and post-occlusive (1 min) reactive hyperaemia. Laser Doppler flux was also recorded during venous occlusion. The basal capillary blood cell velocity and laser Doppler flux values increased significantly (p<0.05) during=" the=" observation=" period.=" the=" time=" to=" maximal=" capillary=" blood=" cell=" velocity=" during=" hyperaemia=" was=" prolonged=" 2=" months=" after=" combined=" kidney=" and=" pancreas=" transplantation="><0.05), and=" still=" more=" so=" at=" 38=" months="><0.05). the=" ability=" to=" decrease=" blood=" flow=" during=" venous=" occlusion=" was=" impaired=" at=" 2=" months,=" and=" was=" not=" significantly=" better=" at=" reinvestigation.=" the=" results=" indicate=" a=" succesive=" increase=" of=" basal=" blood=" flow=" in=" the=" skin=" microcirculation=" after=" successful=" combined=" kidney=" and=" pancreas=" transplantation,=" but=" no=" improvement=" of=" the=" impaired=" microvascular=">     

肾移植患者巨细胞病毒感染的临床观察

目的 :明确肾移植患者术前巨细胞病毒 (CMV)感染的发生率和术后活动性CMV感染的发生规律。　 方法 :检测 2 7例健康成人 ,以及我院 2 0 0 2年 3月～ 2 0 0 3年 6月期间 1 38例尿毒症患者肾移植前血清抗CMV抗体 (抗CMV IgG、CMV IgM ) ;观察肾移植后CMV pp6 5抗原血症的动态变化。　 结果 :2 7例健康成人血清抗CMV IgM均为 (- )、抗CMV IgG的 (+)率为 73 9%、外周血CMV pp6 5阳性白细胞数为 0～ 4个 / 5× 1 0 4WBC ;尿毒症患者术前CMV IgG、CMV IgM阳性率分别为 93 5 %、7 1 % ,肾移植后外周血CMV pp6 5 (+)白细胞数为 0～ 2 2 80个 / 5× 1 0 4WBC(其中 >5个 / 5× 1 0 4WBC者占 87 0 % )、其高峰期在术后第 6～ 8周。　 结论 :肾移植患者术前CMV感染发生率明显高于健康人群 ,且至少有 7 1 %存在着活动性CMV感染 ;肾移植后 6个月内 ,活动性CMV感染发生率高达87 0 % ;术后第 6～ 8周是活动性CMV感染最严重的时期     

Postabsorptive muscle protein metabolism in type 1 diabetic patients after pancreas transplantation

Insulin was shown to induce protein anabolism in vivo mainly by inhibiting proteolysis. Heterotopic pancreas transplantation in type 1 diabetes mellitus is characterized by peripheral hyperinsulinemia due to systemic rather than portal insulin delivery. Therefore, we studied the postabsorptive muscle protein metabolism in type 1 diabetic patients with or without pancreas transplantation. The forearm balance technique was performed in 9 type 1 diabetic patients on exogenous insulin treatment, in 4 type 1 diabetic patients following successful pancreas transplantation and in 6 healthy volunteers. Labelled leucine and phenylalanine were infused to quantify whole-body and muscle protein synthesis, respectively. In the postabsorptive state, whole-body protein synthesis (leucine kinetics) was similar in pancreas-transplanted patients and controls. In contrast, muscle protein synthesis tended to be less negative in pancreas-transplanted patients with respect to type 1 diabetic patients and healthy volunteers. The present data suggest that recipients with peripheral insulin delivery and chronic hyperinsulinemia are characterized by a preferential stimulation of protein synthesis in muscle rather than in the splanchnic district. When insulin was infused acutely, while maintaining euglycemia, the whole-body and muscle protein synthesis rates were approximately halved in type 1 diabetic patients with and without pancreas transplantation. We conclude that pancreas transplantation is able to normalize basal and insulin-stimulated protein metabolism. Chronic hyperinsulinemia counteract steroid-induced protein degradation by means of a mild, but persistent stimulation of muscle protein synthesis. Accepted in revised form: 1 March 2001     

Cross-sectional study of peripheral microcirculation in diabetic patients with microangiopathy: influence of pancreatic and kidney transplantation

Diabetic vascular lesions and peripheral autonomic neuropathy are both closely linked to long-term metabolic control of diabetes. Transcutaneous oxygen tension (P _tcO₂) measurements were made to elucidate whether autonomic neuropathy disturbs the cutaneous microciculatory blood flow, and whether long-term glucose normalization ameliorates such impairment. Twenty-eight type 1 (insulin-dependent) diabetic patients in whom clinically significant macroangiopathy had been excluded by angiography were studied, subdivided into group An=14; before simultaneous pancreas/kidney transplantation (SPKT); mean age 35 years, range 22–51 years; mean duration of diabetes 24 years, (range 15–32) years and group B (n=14; mean 31 months, range 2–101 months, after successful SPKT; mean age 35 years, range 19–56 years; mean duration of diabetes 22 years, range 14–29 years). On addition there was a group (group C) of age-and sex-matched healthy control subjects (n=14; mean age 35 years, range 23–62 years).P _tcO₂ measurements included basal recordings at 44°C on the leg and the foot, functional recordings at 44°C after arterial occlusion of the limb for 4 min, measurements during breathing 5 l oxygen per minute and finally while standing up (stand up dP ₅₀/dt). All subjects underwent extensive cardiac autonomic testing. In this cross-sectional study the recordings of basal values and of the functional parameters after arterial occlusion and during breathing oxygen did not differ significantly between groups A, B and C. The stand-up dP ₅₀/dt values were not significantly different between groups A and B (0.43±0.02 vs 0.47±0.03 mmHg/s, mean ± SEM); but A+B values were significantly higher than in C (0.22±0.01 mmHg/s;P<0.001). These values were correlated significantly with all parameters of cardiac autonomic neuropathy (r range–0.56 to –0.88;P<0.001). It may be concluded that normalization of blood glucose by pancreatic transplantation is not able to ameliorate peripheral microcirculation, but that measurement of transcutaneous oxygen tension is a possible new technique for quantifying alterations in the venoarteriolar reflex in peripheral diabetic autonomic neuropathy that lead to disturbed peripheral microcirculation in diabetic patients.     

肌电电生理诊断糖尿病早期周围神经病变的敏感指标探讨

本文报道了１７１例糖尿病患者通过肌电图电生理检查，测定运动和感觉传导速度及胫神经Ｈ反射的结果，并分析了临床症状，发现糖尿病周围神经病１１６例（６７．８％），其中单纯Ｈ反射异常２７例，神经传导异常兼有或无Ｈ反射异常８９例，提出了诊断糖尿病性周围神经病电生理检查最敏感的指标，并探讨了神经传导与年龄、病程、空腹血糖、果糖胺及ＨｂＡｌｃ之间的相互关系。     

肾移植后输尿管外科并发症

连续９６９例尸体肾移植中，有３３例术后发生输尿管并发症，其中尿漏与输尿管梗阻分别为２１例和１２例。有１１例膀胱输尿管吻合口漏与５例输尿管梗阻在术后早期发生，均与手术操作不当有关，早期手术探查解除诱因后均获治愈。１０例因输尿管坏死导致输尿管缺损尿漏，其中３例在术后２．５－４个月发生输尿管坏死，可能与输尿管排异有关。根据输尿管残留长度分别采用不同的手术方法，替代和弥裤输尿管短缺。８例获得治愈，术后发生     

糖尿病神经病变中的免疫机制

越来越多的研究证实，免疫因素参与了糖尿病神经病变，尤其是糖尿病腰骶神经根病、单神经病和远端对称性多神经病的发病过程。该文对糖尿病神经病变可能涉及的免疫因素进行了综述。     

Metabolic control and progression of complications in insulin-dependent diabetic patients after kidney transplantation.

Patient survival and progression of complications were monitored for 3 years after kidney transplantation in 29 type-1 diabetic patients. Ten age-matched, non-diabetic kidney-transplanted patients served as controls. Five diabetic patients died during follow-up (three cardiovascular events, two infections), three diabetic patients had a non-fatal myocardial infarction and four developed cerebrovascular complications after transplantation. Of the diabetic patients, 69% suffered from proliferative retinopathy before transplantation; 20% of them improved, 65% remained unchanged and 15% deteriorated after transplantation. Motor but not sensory conduction velocity measured from the nervus medianus improved after transplantation. Autonomic neuropathy was observed in 50% of the patients and was unaffected by transplantation. Glycaemic control did not improve significantly during follow-up (HbA1, 10.6 +/- 0.5% before and 9.5 +/- 0.6% 3 years after transplantation). Body weight increased in both diabetic and non-diabetic patients within 3 years after transplantation (from 68 +/- 2 to 77 +/- 6 kg in diabetics, P less than 0.01; from 167 +/- 4 to 77 +/- 6 kg in non-diabetics, P less than 0.01). Subcutaneous fat thickness measured from computer tomography scans of the calf increased in diabetic patients from 5.0 +/- 0.6 to 6.1 +/- 0.9 mm (P less than 0.05). However, the cross-sectional areas of triceps and calf muscles did not increase, suggesting that the increase in body weight was solely due to an increase in fat. It is clear that diabetes-related complications continue to progress and are not influenced by a successful kidney transplant.     

Rehabilitation and quality of life in diabetic patients after successful pancreas-kidney transplantation

Twenty-seven Type I diabetic patients in end-stage renal failure were followed after combined pancreas-kidney transplantation. All patients received duct-occluded segmental pancreas grafts. Clinical progression of extrarenal diabetic complications was studied in 11 patients with long-term functioning pancreatic and renal transplants (Group 1), and in 16 patients who had lost pancreatic graft function, but retained renal graft function (Group 2). Pretransplant, extrarenal diabetic complications were equally distributed in the two groups. In the follow-up period, however, the progress of these complications was less severe in patients with functioning pancreatic transplants. No differences were found between the groups concerning rehabilitation, working capacity, need of help or hospital admittance. It is suggested that pancreas transplantation performed in an earlier stage of diabetes before serious complications have developed, would probably improve rehabilitation and quality of life in these patients.     

Diabetic microangiopathy in Type 1 (insulin-dependent) diabetic patients after successful pancreatic and kidney or solitary kidney transplantation

To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulin-dependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n=17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow / velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46±2 mm Hg to 63±3 mmHg), reoxygenation time (fall from 224±12s to 114±6s) and laser speckle measurement (rise from 4.2±1.7 to 5.6±1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation.     

Recent developments in pancreatic transplantation

At this moment there are more than 10,000 pancreases transplanted into those with diabetes mellitus worldwide. The introduction of new immunosuppressants and refined technical procedures have resulted in a survival of 90% of the grafts and patients. In most cases a simultaneous kidney transplant is performed in patients requiring haemodialysis or peritoneal dialysis. This results in a normal daily life without insulin injections or dialysis treatment. A successful pancreas transplantation in combination with a kidney transplantation can protect the transplanted kidney from diabetic changes. The day in, day out, quality of life of these patients is dramatically increased. The longest pancreas transplant known to be still working is now more than 20 years old. The results from the DCCT study (1) are demonstrating that tight blood sugar control, in those with type I diabetes reduces the complications of diabetes. This is best accomplished by transplanting pancreas grafts into diabetic patients.     

Current aspects of renal dysfunction after liver transplantation

The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.     

Non-invasive and quantitative assessment of sudomotor function for peripheral diabetic neuropathy evaluation

Aims

Perturbation of pain sensation is considered one of the major initiating risk factors for diabetic foot ulcer. Sweat dysfunction leading to abnormal skin conditions, including dryness and fissures, can increase foot ulcer risk. The aim of this study was to evaluate Sudoscan™, a new, quick, non-invasive and quantitative method of measuring sudomotor dysfunction as a co-indicator of the severity of diabetic polyneuropathy (DPN).

Methods

A total of 142 diabetic patients (age 62 ± 18 years, diabetes duration 13 ± 14 years, HbA_1c 8.9 ± 2.5%) were measured for vibration perception threshold (VPT), using a biothesiometer, and for sudomotor dysfunction, using electrochemical sweat conductance (ESC) based on the electrochemical reaction between sweat chloride and electrodes in contact with the hands and feet. Retinopathy status was also assessed, as well as reproducibility between two ESC measurements and the effect of glycaemia levels.

Results

ESC measurements in the feet of patients showed a descending trend from 66 ± 17 μS to 43 ± 39 μS, corresponding to an ascending trend in VPT threshold from < 15 V to > 25 V (P = 0.001). Correlation between VPT and ESC was −0.45 (P < 0.0001). Foot ESC was lower in patients with fissures, while VPT was comparable. Both VPT and foot ESC correlated with retinopathy status. Bland–Altman plots indicated good reproducibility between two measurements, and between low and high glycaemia levels.

Conclusion

Sudoscan™ is a reproducible technique with results that are not influenced by blood glucose levels. Sweating status may be a quantitative indicator of the severity of polyneuropathy that may be useful for the early prevention of foot skin lesions.