During the past 30 years pancreas transplantation evolved into a routine procedure especially suitable for type 1 diabetic recipients undergoing simultaneously kidney transplantation significantly improving quality of life and life expectancy as compared with kidney only recipients. It provides insulin independence with near-normal glucose control without special dietary restriction, freedom from hypoglycemia and chance for halting or regression of microangiopathic diabetes complications. As a separate procedure, pancreas transplantation is carried out mainly in selected subjects suffering from severe hypoglycemic episodes and impaired hypoglycemia awareness or as a subsequent procedure in type 1 diabetic kidney recipients from both cadaveric or living donors. Five-year insulin independence rate following combined pancreas and kidney, pancreas only and pancreas after kidney procedures currently exceed 75, 50 and 62 %, respectively. Though the outcomes still continue to improve, the rate of pancreas transplants has reached a plateau in several European countries or even declines in the United States. Main reasons for that include fewer referrals from diabetes specialist, decreased donor quality, introduction of islet transplantation as a less invasive procedure but probably most of all probably insufficient information on the latest progress and trends achieved in this area. In the area of transplant therapy of diabetes Czech Republic traditionally ranks to the most active countries providing different transplant options according to individual clinical needs including islet transplantation.

• MeSH
• Diabetes Mellitus, Type 1 surgery   MeSH
• Diabetic Nephropathies surgery   MeSH
• Hypoglycemia MeSH
• Quality of Life MeSH
• Humans MeSH
• Islets of Langerhans Transplantation MeSH
• Kidney Transplantation MeSH
• Pancreas Transplantation * statistics & numerical data   MeSH
• Living Donors MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

• Keywords
• biomarkers, chronic kidney disease, diabetic nephropathy, diagnosis, urine proteomics,
• MeSH
• Diabetes Mellitus, Type 2 complications   diagnosis   urine   MeSH
• Diabetic Nephropathies diagnosis   etiology   urine   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Peptidomimetics urine   MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Proteomics methods   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Validation Study MeSH
• Names of Substances
• Peptidomimetics MeSH

AIMS: Diabetes mellitus and decreased renal function are important risk factors for contrast-induced nephropathy (CIN) in which oxidative stress damage may play a role. Alkalinization with sodium bicarbonate (NaHCO₃) has been proposed as a means of reducing free-radical mediated renal injury; however, the effectiveness of NaHCO₃ treatment to prevent CIN in high-risk patients remains uncertain. METHODS: We performed a prospective, randomized, double blind, sodium chloride (NaCl) hydration-controlled study of NaHCO₃ in 120 diabetic patients with impaired renal function (serum creatinine ≥100 μmol/L) undergoing an elective procedure with use of low-osmolar contrast media. The primary endpoint was the incidence of CIN defined as creatinine increase of ≥25% and/or ≥44 μmol/L within 2 days after contrast. Secondary end-points were maximal changes in serum creatinine and estimated glomerular filtration rate. Urine F₂-isoprostane levels were also assessed as measure of oxidative stress. RESULTS: There were no significant group differences in baseline characteristics except for the marginally lower age of the NaHCO₃ treated patients (63 ± 11 vs. 67 ± 10 years; p=0.05). CIN occurred in 7 (11.5%) and 5 (8.5%) patients of the NaHCO₃ and NaCl groups, respectively (p=0.76; incidence rate ratio 1.35; 95% CI 0.37-5.41). No significant differences were seen in secondary outcome measures and changes in the parameter of oxidative stress. CONCLUSIONS: In diabetic patients with renal function impairment sodium bicarbonate does not confer protection against contrast-induced nephropathy greater than sodium chloride-based hydration. Its specific role in mitigating oxidative stress damage in CIN is also not supported by our data.

• Keywords
• Contrast-induced nephropathy, Diabetes mellitus, Impaired renal function, Sodium bicarbonate,
• MeSH
• Sodium Chloride therapeutic use   MeSH
• Diabetic Nephropathies chemically induced   drug therapy   MeSH
• Double-Blind Method MeSH
• Sodium Bicarbonate therapeutic use   MeSH
• Contrast Media adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Sodium Chloride MeSH
• Sodium Bicarbonate MeSH
• Contrast Media MeSH

BACKGROUND: BK virus (BKV) replication is considered as a marker of risk for polyomavirus BK-associated nephropathy (PVAN). We evaluated the occurrence and risk factors for BKV DNA positivity following simultaneous pancreas/kidney transplantation (SPK). METHODS: Point prevalence of BK viruria and viremia was assessed in 183 SPK recipients. Real-time polymerase chain reaction was used with a detection threshold of 10(3) copies/mL. High-level BKV positivity was defined as viruria and/or viremia >10(7) and >10(4) copies/mL, respectively. BKV-positive patients were retested after 4-13 months and underwent an additional six-month clinical follow-up. RESULTS: Urine and serum BKV positivity was detected in 28 (17.3% of available samples) and 7 (3.8%) patients, with high-level viruria and viremia occurring in 6 (3.7%) and 3 (1.6%) patients, respectively. PVAN was biopsy-confirmed in 1 and suspected as a cause of progressive renal failure in another SPK recipient. Patients with single low-level viruria did not progress to high-level positivity or PVAN at follow-up. In multivariate analysis, pre-transplant diabetes duration and delayed graft function were independently associated with BKV positivity. CONCLUSIONS: Point prevalence of high-level BKV positivity and PVAN was low in SPK recipients from a single center. Diabetes duration and delayed graft function were independent risk factors for BKV replication.

• MeSH
• DNA, Viral blood   MeSH
• Adult MeSH
• Tumor Virus Infections diagnosis   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Diseases diagnosis   etiology   MeSH
• Polyomavirus Infections diagnosis   MeSH
• Virus Replication * MeSH
• Risk Factors MeSH
• Kidney Transplantation adverse effects   MeSH
• Pancreas Transplantation adverse effects   MeSH
• Viremia diagnosis   MeSH
• Viral Load * MeSH
• BK Virus isolation & purification   physiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA, Viral MeSH

BACKGROUND: Malakoplakia is an unusual chronic inflammatory disease with distinctive histopathological features rarely involving the parenchyma of a transplanted kidney, and to date less than ten cases have been reported. METHODS AND RESULTS: We present a case of malakoplakia of a kidney graft in a 31 year old woman after simultaneous kidney and pancreas transplantation, which was successfully treated with quinolones. After the treatment of malakoplakia, she was monitored regularly, and her renal and pancreas grafts functioned well for the following 9 years, which is 12 years post transplantation. Moreover, 1 year after treatment of malakoplakia she became pregnant and gave birth to a healthy child. CONCLUSION: Evaluation of a kidney biopsy sample represents the key to diagnosis of malakoplakia which is important for correct patient management. Treatment with antibiotics with intracellular penetration (quinolone type) may result in curing the disease. According to our knowledge, this is the first case of allograft renal malakoplakia after combined kidney and pancreas transplantation.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Quinolones therapeutic use   MeSH
• Diabetes Mellitus, Type 1 surgery   MeSH
• Adult MeSH
• Humans MeSH
• Malacoplakia diagnosis   drug therapy   etiology   MeSH
• Kidney Diseases drug therapy   etiology   MeSH
• Kidney Transplantation adverse effects   MeSH
• Pancreas Transplantation MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Quinolones MeSH

Evaluation of: Tavakoli M, Kallinikos P, Iqbal A et al. Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabet. Med. 28(10), 1261-1267 (2011). A recent observational study has evaluated whether a novel examination method, corneal confocal microscopy, can be used to detect changes in corneal nerve morphology following improvements of conventional risk factors in diabetic patients with mild-to-moderate neuropathy. At 2-year follow-up, improvement of glycemic control (HbA1c) correlated significantly with increases in corneal nerve fiber density. The results add new supportive evidence to data from previous studies of corneal confocal microscopy for its potential use as a convenient noninvasive technique in trials of therapeutic interventions for diabetic neuropathy. Since so far only intensive glycemic control has been proven as an effective measure, this could represent an important advance in the search for new treatment options for this major diabetic complication.

• Keywords
• corneal confocal microscopy, corneal nerves, diabetic neuropathy, risk factors,
• Publication type
• Journal Article MeSH

OBJECTIVE: To assess the effect of normoglycemia following simultaneous pancreas/kidney transplantation (SPK) on neurological function and intraepidermal nerve fiber density (IENFD) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We performed vibration perception threshold (VPT) testing and autonomic function testing (AFT) and assessed IENFD in skin biopsies from the lower thigh and upper calf in 14 healthy control subjects and 18 patients with type 1 diabetes at the time of and at 21-40 (median 29) months post SPK. RESULTS: At baseline, significantly increased VPTs, pathological AFT results, and severe reduction in IENFD were present in SPK recipients. After SPK, an increase of IENFD in the thigh of more than one epidermal nerve fiber per millimeter was noted in three patients (median 4.1, range 1.9-10.2), but changes were not significant for the group as a whole. CONCLUSIONS: We conclude that either irreversible nerve damage might be present in some SPK recipients or that longer periods of normoglycemia might be needed to allow nerve regeneration.

• MeSH
• Diabetes Mellitus, Type 1 blood   pathology   physiopathology   surgery   MeSH
• Diabetic Nephropathies blood   pathology   surgery   MeSH
• Diabetic Neuropathies pathology   MeSH
• Adult MeSH
• Biopsy, Needle MeSH
• Blood Glucose metabolism   MeSH
• Skin innervation   pathology   MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Nerve Fibers physiology   MeSH
• Perception MeSH
• Prospective Studies MeSH
• Reference Values MeSH
• Kidney Transplantation * MeSH
• Pancreas Transplantation * MeSH
• Vibration MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Blood Glucose MeSH

Polyomavirus-associated nephropathy (PVAN) has emerged as an important cause of graft loss following kidney transplantation. Experience with kidney retransplantation (reKT) in PVAN is very limited, especially in the setting of uninterrupted immunosuppression protecting the still functioning pancreatic graft after simultaneous pancreas/kidney transplantation (SPK). We present a review of five cases of reKT in four SPK recipients with Type 1 diabetes mellitus from a single centre (a second reKT was performed in one patient following first reKT failure due PVAN recurrence). Pre-emptive nephrectomy of the failed graft was performed in three of the cases and all kidney grafts for reKT were harvested from cadaveric donors. All patients are dialysis- and insulin-independent at 30 (9-55), median (range), months following last reKT with maintenance immunosuppression consisting of tacrolimus/sirolimus in three and cyclosporine A/mycophenolate mofetil in one patient. In conclusion, reKT represents an effective treatment option in SPK patients with kidney failure on account of PVAN. Use of interventions designed to reduce active viral replication, including pre-emptive nephrectomy of the failed graft, should be considered before reKT.

• MeSH
• Adult MeSH
• Immunosuppression Therapy MeSH
• Tumor Virus Infections * MeSH
• Kidney virology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Diseases surgery   virology   MeSH
• Polyomavirus Infections * MeSH
• Polyomavirus * MeSH
• Graft Survival * MeSH
• Reoperation MeSH
• Retrospective Studies MeSH
• Kidney Transplantation * MeSH
• Pancreas Transplantation MeSH
• Transplants MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Diabetic peripheral neuropathy is the most common complication of long-standing diabetes mellitus which frequently results in clinically significant morbidities e.g. pain, foot ulcers and amputations. During its natural course it progresses from initial functional changes to late, poorly reversible, structural changes. Various interconnected pathogenetic concepts of diabetic neuropathy have been proposed based on metabolic and vascular factors, mostly derived from long-term hyperglycemia. These pathogenetic mechanisms have been targeted in several experimental and clinical trials. This review summarizes available, mainly morphological data from interventions designed to halt the progression or achieve the reversal of established diabetic neuropathy, which include the recovery of normoglycemia by pancreas or islet transplantation, polyol pathway blockade by aldose reductase inhibitors, mitigation of oxidative stress by the use of antioxidants or correction of abnormalities in essential fatty acid metabolism. Unfortunately, to date, no treatment based on pathogenic considerations has shown clear positive effects and thus early institution of optimal glycemic control remains the only available measure with proven efficacy in preventing or halting progression of diabetic neuropathy. Further experimental and clinical research employing objective reproducible parameters is clearly needed. Novel non-invasive or minimally invasive methods e.g. corneal confocal microscopy or epidermal nerve fiber counts may represent potentially useful instruments for the objective assessment of nerve damage and monitoring of treatment effects.

• Publication type
• Journal Article MeSH

Charcot's or neuropathic osteoarthropathy is one of the most debilitating orthopedic sequelae of diabetes mellitus. Distinguishing Charcot's neuroarthropathy from clinically similar conditions may be challenging. The neurovascular theory postulates that Charcot's neuroarthropathy may be secondary to sympathetic denervation of the lower-extremity vasculature. A convenient method for assessing autonomic neuropathy in patients with Charcot's neuroarthropathy is needed. Short-term power spectral analysis (PSA) of heart rate variability (HRV), a noninvasive and quantitative method for assessing autonomic neuropathy, may be advantageous compared with the traditionally used Ewing's cardiovascular reflex tests. However, there are limitations to the clinical use of PSA of HRV because of poor standardization. We standardized PSA of HRV and assessed autonomic neuropathy in 17 people with acute Charcot's neuroarthropathy using PSA of HRV versus Ewing's tests. More patients with Charcot's neuroarthropathy were diagnosed as having autonomic neuropathy with PSA of HRV than with Ewing's tests (94% versus 82%); however, no significant difference between the two methods was found. The results of this study suggest that PSA of HRV requires minimal patient collaboration and time expenditure compared with Ewing's tests and may be useful in detecting autonomic neuropathy in patients with Charcot's neuroarthropathy.

• MeSH
• Diabetic Neuropathies physiopathology   MeSH
• Electrocardiography, Ambulatory * MeSH
• Middle Aged MeSH
• Humans MeSH
• Autonomic Nervous System Diseases diagnosis   physiopathology   MeSH
• Arthropathy, Neurogenic physiopathology   MeSH
• Heart Rate physiology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH