[Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment]. / Refeeding-Syndrom : Pathophysiologie, Risikofaktoren, Prophylaxe und Therapie.

Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role. Since refeeding syndrome is not well known and the symptoms can be extremely heterogeneous, this complication is poorly recognized, especially against the background of severe disease and multimorbidity. This overview aims to summarize the current knowledge and increase awareness about refeeding syndrome.

Structural and Functional Adaptation of the Remnant Kidney After Living Kidney Donation: Long-Term Follow-up.

OBJECTIVE: Several adjustments occur after nephrectomy (NT) in the donor's remnant kidney. We investigated kidney donors 10 years after NT and compared several parameters before and after transplantation. METHODS: A total of 42 kidney donors of the University of Luebeck's Transplant Center were scheduled for a 10-year follow-up and were offered several investigations: laboratory tests, urinalysis and kidney ultrasound examination including determination of kidney volume (KV), resistive index (RI) and pulsatility index (PI). Moreover, a 24-hour ambulatory blood pressure monitoring (ABPM) was performed. A review of the medical records allowed comparison of the investigated parameters before (t0), 1 month after (t0.1), and 10 (t10) years after NT. RESULTS: Creatinine clearance decreased from 94.3 ± 23 (t0) to 52.4 ± 22 mL/min/1.73 m2 (t0.1) and increased to 78.2 ± 19 mL/min/1.73 m2 after 10 years (t10). Tubular proteinuria (α1-microglobuline) increased from 6.1 ± 1.5 (t0) to 63 ± 4.8 (t0.1) (P < .05) and decreased to 36 ± 2.4 mg/g creatinine at t10 (P < .05). Ultrasound examinations revealed a growth of the KV from 159.8 ± 23.1 (t0) to 175.5 ± 22.1 mL (t10) (P < .05) and an increase of RI and PI from t0 of 0.63 ± 0.01 and 1.03 ± 0.03 to t10 of 0.72 ± 0.04 (P < .05) and 1.24 ± 0.11 (P < .05), respectively. Post-NT ABPM values were not significantly different from pre-NT values. CONCLUSIONS: NT leads to hypertrophy of the remnant kidney associated with an increase of organ volume and creatinine clearance after 10 years of follow-up. Our results indicate an excellent prognosis for the kidney donors without any signs of renal damage.

Strength and endurance training in the treatment of lung cancer patients in stages IIIA/IIIB/IV.

PURPOSE: This randomized controlled trial tested the effects of a specially designed strength and endurance training on the independence and quality of life in lung cancer patients in stages IIIA/IIIB/IV during palliative chemotherapy. METHODS: Between August 2010 and December 2011, 46 patients were randomized into two groups receiving either conventional physiotherapy or special physiotherapeutic training. The Barthel Index served as primary endpoint. The secondary endpoints were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C-30/LC-13) questionnaire, the 6-Minute Walk Test (6MWT), stair walking, the Modified Borg Scale, and muscle strength. Nonparametrical data were analyzed with the Wilcoxon and Mann-Whitney U test. For parametric, data student t tests were used. A p value of ≤.05 was accepted. RESULTS: Twenty-nine patients completed the trial (Intervention group (IG), n = 18; control group (CG), n = 11). Significant differences were detectable in the Barthel Index (IGmean = 92.08; CGmean = 81.67; p = .041), in single scores of the EORTC QLQ C-30/LC-13 questionnaire (physical functioning, p = .025; hemoptysis, p = .019; pain in arms or shoulder, p = .048; peripheral neuropathy, p = .050; cognitive functioning, p = .050), in the 6MWT, stair walking, strength capacity, and in the patient's dyspnoea perception during submaximal walking activities (IG > CG). CONCLUSION: According to these findings, lung cancer patients should receive enhanced physical activity intervention during palliative chemotherapy.

[Diabetes and kidneys]. / Diabetes und Niere.

Diabetic nephropathy is the leading cause of end-stage renal disease all over the world. Diagnosis is confirmed by measuring urin albumin excretion and calculated renal function (eGFR). Once the diagnosis is confirmed there should be a search for confounding cardiovascular risk factors and even established cardiovascular disease because of the associated high cardiovascular risk. In type 1 diabetes metabolic control is the main issue. In case of renal impairment and in patients with type 2 diabetes a multifactorial approach is necessary, which consists of dietary advise, metabolic control, lowering elevated blood-pressure, cessation of smoking, ASS and lipid-lowering drug-therapy. Special drugs for the treatment of diabetes-induced renal disease are not available.

Semiconductor quantized voltage source.

We realize and investigate an all-semiconductor quantized voltage source which generates quantized output voltages V(out) = f(h/e) linked only to two fundamental constants, the electron's charge e and Planck's constant h, and to an applied excitation frequency f. The device is based on an integrated quantized circuit of a single-electron pump operated at pumping frequency f and a quantum Hall device monolithically integrated in series. Robust output voltages up to several µV are generated, which are expected to be scalable by orders of magnitude using present technology. The device might open a new route towards the closure of the quantum metrology triangle.

Reduction of gastrointestinal complications in renal graft recipients after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium.

Gastrointestinal (GI) complications such as diarrhea or indigestion frequently occur in renal graft recipients treated with mycophenolate mofetil (MMF), requiring dose reductions to reduce side effects, thereby increasing the risk of rejection episodes and graft loss. In a prospective clinical trial, the immunosuppressive therapy of renal graft recipients was converted from MMF to enteric-coated mycophenolate sodium (EC-MPS) to identify a strategy to reduce GI symptoms without dose reduction. At baseline and 6-8 weeks later patients filled in 4 questionnaires related to GI symptoms and general and health-related quality of life. In 15 German study centers, 196 renal graft recipients (mean age 49.5 ± 13.5 years; male/female, 120/76) were included; 51.0% of patients suffered from GI complications at baseline. The Gastrointestinal Symptom Rating Scale score decreased significantly (P < .001) in patients with GI complications from 2.61 ± 0.86 at baseline to 2.14 ± 0.86 at visit 2. Health-related and general quality of life improved significantly. Fifty percent of patients with GI symptoms and 34% of the total per protocol population reported an improvement of their physical condition after converting the medication. In conclusion, conversion from MMF to EC-MPS reduces GI complications in renal graft recipients, reduces the patients' physical discomfort, and maintains their quality of life. (ClinicalTrials.gov number NCT00149968.).

Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial.

Oral ganciclovir prophylaxis and intravenous preemptive therapy are competitive approaches to prevent cytomegalovirus (CMV) disease after renal transplantation. This trial compared efficacy, safety and long-term graft outcome in 148 renal graft recipients randomized to ganciclovir prophylaxis (N = 74) or preemptive therapy (N = 74). Hierarchical testing revealed (i) patients with CMV infection had more severe periods of impaired graft function (creatinine clearance(max-min) 25.0 +/- 14.2 mL/min vs. 18.1 +/- 12.5 mL/min for patients without CMV infection; p = 0.02),(ii) prophylaxis reduced CMV infection by 65% (13 vs. 33 patients; p < 0.0001) but (iii) creatinine clearance at 12 months was comparable for both regimes (54.0 +/- 24.9 vs. 53.1 +/- 23.7 mL/min; p = 0.92). No major safety issues were observed, and patient survival at 12 months was similar in both groups (5 deaths [6.8%] vs. 4 [5.4%], p = 1.0000). Prophylaxis significantly increased long-term graft survival 4 years posttransplant (92.2% vs. 78.3%; p = 0.0425) with a number needed to treat of 7.19. Patients with donor +/recipient + CMV serostatus had the lowest rate of graft loss following prophylaxis (0.0% vs. 26.8%; p = 0.0035). In conclusion, it appears that routine oral prophylaxis may improve long-term graft survival for most renal transplant patients. Preemptive therapy can be considered in low risk patients in combination with adequate CMV monitoring.

Prospective age-matching in elderly kidney transplant recipients--a 5-year analysis of the Eurotransplant Senior Program.

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

Acute hantavirus infection or renal transplant rejection.

Hantaviruses belong to the so-called emerging pathogens that are transmitted to humans by infected rodents and their excreta. In Central Europe, hantavirus infections usually occur in a mild to moderate form of hemorrhagic fever with renal syndrome. In contrast to the mostly benign or even asymptomatic course of hantavirus infections in previously healthy individuals, the acute hantavirus infection in kidney transplant recipients represents an exceptional situation regarding diagnosis and therapy. We describe the case of a 44-year-old kidney transplant recipient with acute renal transplant failure associated with acute hantavirus infection.

Relationship between donor factors, immunogenic up-regulation, and outcome after kidney transplantation.

Epidemiological data show that the cause of brain death as well as the condition of the organ donor have considerable influence on the outcome of kidney transplantation. An early immunogenic up-regulation, which already exists at the time of organ removal seems to be primarily responsible. So far it has remained unclear which donor factors cause this effect. In a prospective study of 37 organ donors a 0-hour biopsy was performed at the time of explantation to measure the expression of HLA-DR and endothelin-1 (ET-1) immunohistologically using the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. The transplant outcome and the immunohistological results were correlated with various donor factors. Statistically significant correlations were seen with the following parameters: the donor serum creatinine prior to explantation correlated with the incidence of delayed graft function (DGF: 104 +/- 39 vs 78 +/- 35 micromol/L versus no DGF n = 37; P = .043). Early graft loss after transplantation correlated significantly with increased numbers of leukocytes as well as with decreased O2 saturation in the donor immediately before explantation (leucocytes: 16.7 +/- 6.8 vs 12.6 +/- 4.6/nL, n = 37; P = .036; O2 saturation: 94.1% +/- 6.9%, vs 97.7% +/- 2.3%, n = 37; P = .026). Further, donor-independent factors that correlated with acute rejections included cold ischemic time (P = .031), HLA mismatches (P = .028), and occurrence of DGF (P = .033). The degree of HLA-DR expression (range 0 to 2) correlated significantly with early graft loss (2.0 +/- 0.2 vs 1.33 +/- 0.9 for graft function, n = 37; P = .01) as well as the ET-1 expression with DGF (2.0 +/- 0.3 vs 1.5 +/- 0.7 versus no DGF, n = 37; P = .016). In summary, marginal donors should be seen as high immunological risk situations that need careful conditioning.

Cyclosporine C2 levels in de novo renal allograft recipients: a German multicenter prospective observational study.

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C0) and 2-hour postdose (C2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients (n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis. Mean C2 levels (ng/mL), which were measured by liquid chromatography-tandem mass spectrometry at a central laboratory, were: days 3 to 5: 873.1 +/- 391.9; days 7 to 10: 939.1 +/- 422.8; days 14 to 28: 1116.3 +/- 497.6; 3 months: 905.0 +/- 316.8; and after 6 months: 787.0 +/- 276.5. To identify patients at higher risk for acute rejection or allograft dysfunction, we calculated the relative CsA absorption capacity (C2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean values on days 3 to 5: 284.4 +/- 115.1; days 7 to 10: 306.7 +/- 134.8; days 14 to 28: 382.5 +/- 164.7; month 3: 501.5 +/- 168.8; month 6: 512.7 +/- 176.5. Three groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs < 200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350). A between-group comparison of absorption level at 6 months posttransplant revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault formula-based mean glomerular filtration rates of 23.8% and 54.7 +/- 19.0 mL/min, 22.6% and 59.5 +/- 20.7 mL/min, and 17.6% and 67.7 +/- 23.5, respectively. In conclusion, mean C2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA-Abs increasing continuously over the first 6 posttransplant months. High CsA absorbers show a propensity toward good allograft function and lower acute rejection rates at 6 months after renal transplantation.

Laparoscopic fenestration of posttransplant lymphoceles.

BACKGROUND: A lymphocele is a common finding after renal transplantation and occurs in up to 20% of patients. The majority of patients are asymptomatic. However, once a lymphocele has become symptomatic (e.g., through transplant dysfunction) this condition has to be treated. We report our 9-year experience with laparoscopic lymphocele fenestration and discuss the current management options for posttransplant lymphoceles. METHODS: Since 1993, 19 patients (11 males and 8 females; median age 56 years, range 22-68 years) of a total of 31 patients with a symptomatic posttransplant lymphocele have undergone laparoscopic fenestration of their lymphocele at a median of 66 days (range, 19-111 days) following successful renal transplantation in our department. As a first-line treatment, a percutaneous pigtail drainage catheter was inserted in all patients. In case of failure in resolving the fluid collection, the next step included sclerotherapy by instillation of tetracycline or ethanol into the lymphocele cavity in some cases. In patients with a persistent lymphocele, a laparoscopic lymphocele fenestration via a transabdominal approach was undertaken to achieve adequate drainage. RESULTS: Primary laparoscopic lymphocele fenestration was successful in all except two patients, who required a conversion. The median operating time was 36 min (range, 20-70 min). Following the procedure, renal transplant function remained stable or returned to individually normal levels in all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At median follow-up of 27 months, all patients were alive with a functioning transplant. CONCLUSIONS: Laparoscopic lymphocele fenestration is reserved for patients in whom temporary drainage with or without sclerotherapy failed to resolve the fluid collection. In these cases the laparoscopic approach offers obvious technical and clinical advantages compared to open operative techniques.

Hemolytic anemia after kidney transplantation: case report and differential diagnosis.

A 58-year-old woman presented with hemolysis and thrombocytopenia 2 weeks after receiving a kidney graft. Hemolytic uremic syndrome was initially suspected, because in addition to hematological changes the graft function was missing. Unexpectedly, the results of the direct antiglobulin test became positive (4+), which is not normally observed in the hemolytic uremic syndrome. Differentiation of the eluted antibodies revealed anti-rhesus D specificity, which had to be interpreted either as an autoantibody of patient's origin or, hypothetically, as a "graft versus host" antibody of donor origin. Gm- and Km allotyping of these antibodies demonstrated a pattern which differed from the patient's but was identical to that of the kidney donor. Therefore hemolysis could be explained unambiguously by "graft versus host" antibodies. Whether the thrombocytopenia was also due to an immune process was not clear, although some evidence favors this hypothesis. Immunosuppressive treatment remained unchanged and several red blood cell transfusions were necessary before reactivity of the direct antiglobulin test diminished and became negative 7 weeks after kidney transplantation. The occurrence of hemolysis in the early posttransplantation period should thus draw attention to the possibility of "graft versus host" antibodies directed against red cells. Concomitant thrombocytopenia may occur. Donor screening for irregular erythrocyte antibodies should be performed whenever solid organ transplantation is intended.

Laparoscopic nephroureterectomy to exclude upper urinary tract malignancy associated with analgesic nephropathy.

BACKGROUND AND PURPOSE: Analgesic abuse is a potential cause of end-stage renal disease. Such patients bear an elevated risk of developing malignancies, predominantly transitional-cell carcinoma. We report our experience with laparoscopic nephroureterectomy carried out in patients with analgesic nephropathy to exclude upper urinary tract malignancy. All patients were scheduled to be put on the waiting list for cadaveric renal transplantation. PATIENTS AND METHODS: Since 1996, nine women and two men with a long-term history of analgesic abuse have undergone laparoscopic nephroureterectomy at our hospital. The median age was 63 years (range 51-70 years). All patients had developed end-stage renal failure secondary to heavy analgesic abuse with a median duration of 14 years (range 7-40 years). The median interval from the beginning of hemodialysis to laparoscopic nephroureterectomy was 36 months (range 6-76 months). RESULTS: The median operative time was 99 minutes (range 55-170 minutes). There were no conversions to open surgery. Two complications occurred, and three patients required blood transfusions. The median hospital stay lasted 5 days (range 2-12 days), and the median convalescence was 20 days (range 6-44 days). In seven patients, histopathologic examination of the kidney revealed changes attributable to analgesic abuse. None of the patients had a transitional-cell carcinoma, but in two patients, a renal-cell carcinoma stage pT1cN0cM0 grade 2 was detected. CONCLUSION: Patients with analgesic nephropathy bear an elevated risk for the development of transitional-cell or renal-cell carcinoma. In these patients, laparoscopic nephroureterectomy combines minimally operative invasiveness with a maximum of diagnostic safety.

A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients.

BACKGROUND: A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. METHODS: Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. RESULTS: During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. CONCLUSIONS: Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.

Human thiopurine S-methyltransferase activity in uremia and after renal transplantation.

UNLABELLED: In addition to cyclosporin and steroids, azathioprine is frequently used for immunosuppression after renal transplantation. Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. A genetic polymorphism was shown with 1 in 300 homozygous for a TPMT deficiency. These subjects carry the risk of severe myelosuppression when treated with azathioprine. OBJECTIVE: To investigate the influence of hemodialysis on TPMP activity in uremic patients and the effect of azathioprine treatment on enzyme activity. METHODS: The assay for measurement of TPMT activity in packed red blood cells is based on a non-radioactive conversion of 6-thioguanine to 6-methylthioguanine. In 251 patients, TPMT activity was determined before and after a 4-h period of hemodialysis. In 49 patients (26 on azathioprine, 23 on mycophenolate mofetil as control group), TPMT activity was regularly determined during the first 120 days after renal transplantation. RESULTS: TPMT activity is elevated in red blood cells of uremic patients before hemodialysis when compared with TPMT activity after hemodialysis. The latter is comparable to the activity in healthy subjects. In patients treated with azathioprine, the TPMT activity showed a slow increase that declined to pre-treatment values when azathioprine was withdrawn. This could not be observed in patients treated with mycophenolate mofetil. CONCLUSIONS: In uremic patients, TPMT activity is activated by some uremic factors that are removed by hemodialysis. In contrast to what has been observed before, dialysis shifted the TPMT activity close to that of a healthy control group. In patients treated with azathioprine after renal transplantation, the observed increase of TPMT activity could possibly be the result of enzyme induction.

Primary hyperoxaluria type 1 causing end-stage renal disease in a 45-year-old patient.

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.