Refeeding Syndrome in Oncology: Report of Four Cases.

The term refeeding syndrome (RFS) refers to the metabolic perturbations and its attendant complications in subjects who are refed after fasting. The syndrome is characterized by profound shifts of electrolytes and fluids. Its consequences are widespread and sometimes fatal. Patients with malignancies are especially vulnerable due to the presence of multiple comorbidities. We report the course of four patients with malignant or hematological disorders who developed RFS while being treated for their underlying illness. All physicians caring for susceptible patients should be cognizant of the risks of refeeding and treat RFS appropriately to reduce patient morbidity as well as mortality.

"Bowel prep hyponatremia" - a state of acute water intoxication facilitated by low dietary solute intake: case report and literature review.

BACKGROUND: Symptomatic hyponatremia is considered a rare complication of oral bowel preparation for colonoscopy. The pathophysiology underlying this phenomenon has been widely regarded as a mere sequela of excessive arginine vasopressin (AVP) release. CASE PRESENTATION: This case describes a 61-year old woman who developed acute hyponatremic encephalopathy when preparing for elective outpatient lower endoscopy. She had had negligible oral solute intake for two days and ingested four liters of clear fluid within two hours. On admission, the patient was agitated and had slurred speech. Treatment with hypertonic saline lead to full recovery. A brisk aquaresis confirmed acute dilutional hyponatremia. CONCLUSION: Apart from elevated AVP-levels, the amount and speed of fluid intake and concomitant low-solute intake constitute important risk factors in the development of clinically relevant hyponatremias in patients undergoing colonoscopies. Understanding that the cause of sodium imbalance in this scenario is multifactorial and complex is pivotal to recognizing and ideally preventing this complication, for which we propose the term "bowel prep hyponatremia".

A Novel Homozygous SLC2A9 Mutation Associated with Renal-Induced Hypouricemia.

BACKGROUND: Hereditary renal hypouricemia (RHUC) is a genetically heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA; acute kidney injury (AKI) and nephrolithiasis are recognized complications. Type 1 (RHUC1) is caused by mutations in the SLC22A12 gene, whereas RHUC2 is caused by mutations in the SLC2A9 gene. Patient ethnicity is diverse but only few Caucasian families with an SLC2A9 mutation have been reported. METHODS: The current report describes the clinical history, biochemical and molecular genetics findings of a native Austrian family with RHUC2. The propositus presented with 2 episodes of exercise-induced AKI and exhibited profound hypouricemia. Mutational screening of the SLC22A12 and SLC2A9 genes was performed. RESULTS: The molecular analyses revealed the homozygous c.512G>A transition that leads to the p.Arg171His missense substitution in SLC2A9, confirming the diagnosis of RHUC2. Segregation study of the causal mutation revealed that the mother and elder sister were heterozygous carriers, whereas the younger sister was found to be homozygous. CONCLUSION: We report the identification of a novel mutation in SLC2A9 as the cause of RHUC2 in a native Austrian family. We show that glucose transporter 9 mutations cause severe hypouricemia in homozygous individuals and confirm the high risk of AKI in male individuals harbouring these mutations. In our literature review, we provide an overview of the putative underlying pathophysiology, potential renal complications, findings on kidney biopsy as well as potential long-time renal sequelae.

Interfering parameters in the determination of urinary globotriaosylceramide (Gb3) in patients with chronic kidney disease.

INTRODUCTION: Globotriaosylceramide (Gb3, CD77) represents a pivotal part of the cell membrane. Measuring the urinary Gb3 content can be used to screen patients with chronic kidney disease (CKD) for Fabry disease, a disorder caused by hampered Gb3 degradation. However, little is known about factors influencing urinary Gb3 excretion other than Fabry disease. The aim of the present study was to identify routine diagnostic parameters as predictors of urinary Gb3 excretion in patients with CKD. METHODS: Our study included 609 subjects with CKD stage I-V. We analyzed the influence of age, gender, renal function, urinary cell content and chemical characteristics on urinary Gb3 concentrations (total Gb3, Gb3-24 isoform, and Gb3-24:18 isoform ratio), determined by direct electrospray ionization mass spectrometry. RESULTS: In 609 subjects the median total urinary Gb3 was 233 ng/mg and the Gb3-24:18 isoform ratio was 1.2. Twenty-one patients, none of whom had Fabry disease, had a Gb3-24:18 isoform ratio ≥2.3. Females excreted a higher total amount of Gb3, but the Gb3-24:18 isoform ratio was comparable to males. Renal function and age had no influence on total Gb3, Gb3 isoforms or the ratio. Only a distinct load of bacteria and leukocytes was associated with an increased Gb3 excretion. Urinary leukocytes, erythrocytes, bacteria, or protein content did not affect the Gb3-24:18 isoform ratio. CONCLUSION: The Gb3-24:18 isoform ratio is unaffected by several potential influencing variables and may thus be applied for screening for Fabry disease in unselected cohorts of patients presenting with CKD.

Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.

BACKGROUND: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex. METHODS: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression. RESULTS: Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies. CONCLUSION: Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.

Three solid malignancies and a myelodysplastic syndrome with a protracted course after kidney transplantation.

Although a well-known complication after transplantation, multiple non-skin malignancies within a patient are rare. We report on a kidney transplant recipient who over the course of 20 years developed breast cancer twice, a uroepithelial carcinoma, and myelodysplasia transforming into acute leukaemia. Breast cancer was treated as usual. The transitional cell carcinoma was managed with partial cyst ureterectomy with transposition of the native ureter to the graft. Withdrawal of immunosuppression followed under a "watchful waiting" regime. In conclusion, alertness is requested regarding development of malignancies. Creative solutions are necessary in the management of such patients. Under exceptional circumstances, withdrawal of immunosuppression may be an option.

Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria.

The diagnosis of Anderson-Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson-Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers. AGAL activity was determined from filter paper dried blood spots by a fluorescence assay. A positive screening test was defined by an AGAL activity below 1.5 nmol/h/ml. In patients with a positive blood spot-screening test, AGAL activity was re-examined in peripheral blood leukocytes. Genetic testing for mutations in the GLA gene was performed by sequencing to confirm the diagnosis of Anderson-Fabry disease. Two previously not recognized cases with Anderson-Fabry disease were identified. Our study is the first showing that a diagnosis of Anderson-Fabry disease can be missed even in patients who undergo kidney transplantation. Case-finding strategies may be considered a useful tool for diagnosis of this rare disease that may be somewhat more prevalent among kidney transplant recipients compared with dialysis populations.

[Peritoneal dialysis in patients with polycystic kidney disease]. / Peritonealdialyse bei Patienten mit Polyzystischer Nierendegeneration.

In Austria, patients with end-stage renal disease caused by polycystic kidney disease are less frequently treated with peritoneal dialysis (PD) than patients with noncystic renal diseases (6% versus 8%). In contrast, the United States renal data system reports that more than one fifth of patients with polycystic kidney disease choose PD as their initial form of renal replacement therapy. The reasons for this difference are unknown. Extrarenal manifestations of the disease, such as diverticulosis, development of hernias or vascular aneurysms, may theoretically promote the occurrence of complications typically related to PD. However, studies undertaken to clarify these questions did not find any difference in the rates of peritonitis caused by diverticulosis or Gram-negative bacteria, and no differences were seen with respect to vascular complications. Nevertheless, in comparison with the general population, patients with polycystic kidney disease are more likely to develop hernias, and the incidence of herniation may be further increased by PD. In conclusion, patients with polycystic kidney disease who also have abdominal complaints such as meteorism and discomfort, or lumbago resulting from the markedly enlarged kidneys, should not be actively advised to have PD treatment. The same is true for patients with recurrent hernias. However, the technical survival, quality of dialysis, duration of therapy and rates of complications in PD are comparable in patients with cystic or noncystic kidney disease, and therefore all patients with polycystic kidney disease who do not have abdominal complaints or history of recurrent hernias should be informed that PD is an adequate form of renal replacement therapy, equally effective as hemodialysis.

Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for alpha-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.

Magnetic resonance imaging of the peritoneal cavity among peritoneal dialysis patients, using the dialysate as "contrast medium".

The objectives of this study were to evaluate whether adequate observation of abdominal pathologic features related to peritoneal dialysis (PD) was possible with magnetic resonance imaging (MRI) under routine conditions, i.e., against the background of the dialysate and without contrast medium. For 16 male and seven female patients (mean age, 51.8 +/- 15.0 yr; mean duration of PD, 324 +/- 542 d), 25 peritoneal MRI studies were performed with the intraperitoneal dialysate as usual. Indications were symptoms or combinations of symptoms, such as leakage or abdominal wall edema (n = 3), bloody dialysate (n = 4), suspected herniation (n = 1), suspected ultrafiltration failure (n = 2), and abdominal pain (n = 5), or routine assessment after initiation of PD (n = 12). The MRI protocol, which was performed with a 1.0-T scanner, consisted of breath-hold, coronal and transverse, T2-weighted, half-Fourier single-shot turbo spin-echo sequences, using a standard body-array coil. MRI studies were well tolerated and successfully completed for all except two patients. Results indicated a leak along the catheter (n = 1), a leak in an umbilical hernia (n = 1), suspected leakage (n = 1), hernias (n = 5, in three patients), intraperitoneal adhesions (n = 5, in four patients), a ruptured ovarian cyst (n = 1), and pleural effusions (n = 4). Pathologic findings unrelated to PD or located extra-abdominally were observed in 19 of the 25 studies. The catheter tip position was easily identified for all patients. In conclusion, this first report on peritoneal MRI using only dialysate as the "contrast medium" indicates that MRI permits detailed observation of all relevant, PD-related, abdominal pathologic features against the dialysate background, thus avoiding system contamination (and thus the risk of peritonitis).