Friedrich Prischl

Low-GDP fluid (Gambrosol trio®) attenuates decline of residual renal function in PD patients: a prospective randomized study

BACKGROUND Residual renal function (RRF) impacts outcome of peritoneal dialysis (PD) patients. Some PD fluids contain glucose degradation products (GDPs) which have been shown to affect cell systems and tissues. They may also act as precursors of advanced glycosylation endproducts (AGEs) both locally and systemically, potentially inflicting damage to the kidney as the major organ for AGE elimination. We conducted a clinical study in PD patients to see if the content of GDP in the PD fluid has any influence on the decline of the residual renal function. METHODS In a multicentre approach, 80 patients (GFF > or = 3 mL/min/1.732 or creatinine clearance > or =3 mL/min/1.73 m(2)) were randomized to treatment with a PD fluid containing low levels of GDP or standard PD fluid for 18 months. RRF was assessed every 4-6 weeks. Fluid balance, mesothelial cell mass marker CA125, peritoneal membrane characteristics, C-reactive protein (CRP), total protein, albumin, electrolytes and phosphate were measured repeatedly. RESULTS Data from 69 patients revealed a significant difference in monthly RRF change: -1.5% (95% CI = -3.07% to +0.03%) with low GDP (43 patients) vs -4.3% (95% CI = -6.8% to -2.06%) with standard fluids (26 patients) (P = 0.0437), independent of angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker medication. Twenty-four-hour urine volume declined more slowly with low-GDP fluid compared to standard fluids (12 vs 38 mL/month, P = 0.0241), and monthly change of phosphate level was smaller (+0.013 vs +0.061 mg/dL, P = 0.0381). CONCLUSIONS Our prospective study demonstrates for the first time a significant benefit concerning preservation of RRF and urine volume of using a PD fluid with low GDP levels. These findings suggest that GDPs might affect patient outcome related to RRF.

Value of Flumazenil in Benzodiazepine Self-Poisoning

SummaryThe efficacy of the benzodiazepine-antagonist flumazenil (Ro 15-1788) was evaluated in 26 patients with coma due to benzodiazepine self poisoning, alone or in combination with alcohol or other psychoactive drugs. 77% of the patients responded to the administration of a mean dose of 1.73mg (range 0.2 to 8mg) with immediate awakening or an improvement of at least 2 coma grades. In the patients without response (n=3) or with minor improvement (n=3) other psychoactive drugs turned out to be predominantly responsible for their comatose state. Adverse effects offlumazenil treatment such as altered blood pressure or increased heart rate were observed, but were generally mild. An acute benzodiazepine withdrawal syndrome was seen in 2 cases. In conclusion, flumazenil proved to be effective in the treatment of severe benzodiazepine intoxication. Beyond that, in cases of mixed over dosage or initially unknown diagnosis the antidote assisted in the clarification of the clinical condition.

B-immunoblastic lymphoma arising in angioimmunoblastic lymphadenopathy.

We present a female patient with a B-immunoblastic lymphoma of the IgM-lambda type arising in angioimmunoblastic lymphadenopathy. An increased ratio of helper/inducer to suppressor/cytotoxic lymphocytes in the lymph node could have triggered the proliferation of B cells. Evolution of IgM cryoglobulinemia was paralleled by malignant transformation in the lymph node. A short-term in vitro chemosensitivity test could predict response to COP combination chemotherapy suggesting that in vitro chemosensitivity testing can be useful for the therapeutic management of angioimmunoblastic lymphadenopathy.

Diabetes-related end-stage renal disease in Austria 1965–2013

BACKGROUND Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in Austria, accounting for a high burden of morbidity and mortality. In this nationwide study, we aimed to evaluate the incidence and fate of patients with DKD-ESRD over time. METHODS Data (collected annually) from the Austrian Dialysis- and Transplant Registry were analysed for the development of ESRD due to DKD from 1965 to 2013. RESULTS Over 48 years, 8322 and 22 975 patients with ESRD due to diabetes and non-diabetes, respectively, entered dialysis. While DKD-ESRD-patients were not dialysed until 1974, in 1975 seven type 1- and one type 2-diabetics started dialysis (1.06 per million population-PMP). In the mid-eighties, DKD-ESRD-patients increasingly were accepted for dialysis (1986: 14.53 PMP, 1996: 31.16 PMP). After a peak incidence of 415 diabetic ESRD-patients in 2006 (50.19 PMP), numbers decreased continuously thereafter (2013: 299 patients, 35.73 PMP). Mean age at start of dialysis increased over time and was lower in type 1- and higher in type 2- compared with non-diabetic patients. Five-year-survival-probability in two diabetic ESRD-cohorts, starting in 2007/08 and 10 years earlier was calculated. Five-year-survival was 28% in 1997/98 and 37.5% in 2007/08. Adjusted relative risk reduction was 33% (HR 0.67, CI 95% 0.57-0.78; P < 0.001). CONCLUSION Despite a growing prevalence of diabetes, the incidence of diabetic ESRD has decreased after 2006. Five-year-survival-probability has improved over 10 years. Multifactorial therapeutic interventions may have resulted in this improvement.

Treatment with Oral Active Vitamin D Is Associated with Decreased Risk of Peritonitis and Improved Survival in Patients on Peritoneal Dialysis

Peritonitis is a major complication of peritoneal dialysis (PD) being associated with hospitalization, catheter loss, technique failure, and increased mortality. Data on incidence rates and risk factors for peritonitis episodes vary between centers. In seven Austrian PD units clinical and laboratory data on each peritonitis episode were collected from all patients (n = 726) who performed PD between January 2000 and December 2009. The peritonitis incidence rate was 0.32 episodes/patient-year. In a multivariate analysis the risk of peritonitis was decreased by 57% in patients treated with oral active vitamin D (HR 0.43; 95% CI 0.28–0.64). Renal disease classified as “other or unknown” (HR 1.65; 95% CI 1.08–2.53) and serum albumin <3500 mg/dl (HR 1.49; 95% CI 1.04–2.15) were also associated with an increased risk of peritonitis. Albumin levels <3500 mg/dl (HR 1.89; 95% CI 1.13–3.17), age (HR 1.06 per year; 95% CI 1.03–1.09), and cardiomyopathy (HR 3.01; 95% CI 1.62–5.59) were associated with increased mortality, whereas treatment with oral active vitamin D was associated with a significantly lower risk of death (HR 0.46; 95% CI 0.27–0.81). In this retrospective multi-center study we identified several factors being related to increased risk of peritonitis in PD patients. Treatment with oral active vitamin D was identified as being independently associated with decreased risk of peritonitis, and decreased all-cause mortality in PD patients.

Beta-2-Microglobulin for Differentiation between Ciclosporin A Nephrotoxicity and Graft Rejection in Renal Transplant Recipients

The clinical relevance of daily measurement of beta 2-microglobulin in serum and urine was evaluated in 49 patients undergoing renal transplantation. The changes in beta 2-microglobulin levels were compared to standard parameters for assessment of renal function. One hundred episodes of acute deterioration of renal function, clinically diagnosed as rejection, were analyzed retrospectively: (1) In 18 episodes renal malfunction did not respond to methylprednisone but improved immediately upon dose reduction of ciclosporin A, thus indicating a nephrotoxic effect of the drug. In these cases a mean increase of beta 2-microglobulin in urine as high as 7.9 mg/l was observed while serum values decreased. (2) Fifty episodes of apparent rejection (responsive to steroids) were preceded by a 3-day lasting continuous rise of beta 2-microglobulin in serum of up to 3.6 mg/l as a mean with only a moderate elevation in urine. (3) In 13 episodes antirejection treatment could have been avoided as continuously declining laboratory parameters indicated spontaneous improvement of renal function. We conclude that parallel determination of beta 2-microglobulin in serum and urine allows to differentiate between ciclosporin A nephrotoxicity and rejection in 91% of the cases.

A COL4A5 mutation with glomerular disease and signs of chronic thrombotic microangiopathy.

COL4A5 mutations are a known cause of Alport syndrome, which typically manifests with haematuria, hearing loss and ocular symptoms. Here we report on a 16-year-old male patient with a negative family history who presented with proteinuria, progressive renal failure and haemolysis, but without overt haematuria or hearing loss. A renal biopsy revealed features of atypical IgA nephropathy, while a second biopsy a year later showed features of focal segmental glomerulosclerosis, but was finally diagnosed as chronic thrombotic microangiopathy. Targeted sequencing of candidate genes for steroid-resistant nephrotic syndrome and congenital thrombotic microangiopathy was negative. Despite all therapeutic efforts, including angiotensin-converting enzyme inhibition, immunosuppressive therapy, plasma exchanges and rituximab, the patient progressed to end-stage renal disease. When a male cousin presented with nephrotic syndrome years later, whole-exome sequencing identified a shared disruptive COL4A5 mutation (p.F222C) that showed X-linked segregation. Thus, mutations in COL4A5 give rise to a broader spectrum of clinical presentation than commonly suspected, highlighting the benefits of comprehensive rather than candidate genetic testing in young patients with otherwise unexplained glomerular disease. Our results are in line with an increasing number of atypical presentations of single-gene disorders identified through genome-wide sequencing.

Interferon alpha-2 for hairy cell leukemia: Evidence for induction of RNA synthesis in hairy cells and failure to correlate enhancement of natural killer cells with elimination of hairy cells

The effect of human recombinant interferon α2 (IFNα2) on hairy cells obtained from 16 patients was evaluated. All patients promptly responded to induction of remission with 2 times 106 U/m2 interferon α2b, three times a week, sc. In order to achieve a more detailed insight into the mode of action of interferon in this disease, we determined the influence of IFNα2 on the incorporation of radiolabeled thymidine and uridine into hairy cells. While both 3H‐thymidine and 3H‐uridine incorporation were unaffected by IFNα2 in a 3‐hour incubation period, a significant increase in uridine incorporation into hairy cells, but not CLL cells, was observed after 24 h. Cell surface marker analysis performed with monoclonal antibodies did not reveal a quantitative alteration of the immunophenotype of hairy cells in vitro. In addition, natural killer cells, assessed by monoclonal antibodies and a cytotoxicity assay against K 562 cells, were found to be decreased in 9 out of 10 patients prior to therapy. Although IFNα2 could stimulate natural killer cells in vivo, we did not find a consistent correlation between the activation of these cells and the response to therapy. We conclude, therefore, that NK cells play no major role in the regression of hairy cells. Furthermore, IFNα2 does not alter antigenic determinants in vitro, but leads to an enhanced incorporation of 3H‐uridine into hairy cells in vitro, thus indicating a possible role for the induction of RNA synthesis in vivo.

Peritoneal dialysis in patients with polycystic kidney disease

SummaryIn 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.ZusammenfassungPatienten mit Polyzystischer Nierendegeneration und terminaler Niereninsuffizienz werden in Österreich zu 6 % und somit seltener der Peritonealdialyse (PD) als Nierenersatztherapie zugeführt als Patienten mit nicht-zystischen Nierenerkrankungen (ca. 8 %). In den USA praktizieren mehr als ein Fünftel der Zystennieren-Patienten PD. Die Gründe für diese Unterschiede sind unklar. Die bei dieser Erkrankung beschriebenen extrarenalen Manifestationen wie Divertikulose, erhöhte Inzidenz der Hernienbildung oder Gefäßaneurysmen könnten theoretisch mit erhöhten Komplikationsraten an der PD verbunden sein. Entsprechende Untersuchungen weisen aber kein erhöhtes Risiko für Peritonitis durch Divertikulose und auch keine an der PD vermehrten Gefäßkomplikationen nach. Hernien dürften unabhängig von der Art der Nierenersatztherapie bei Polyzystischer Nierendegeneration gehäuft auftreten und werden möglicherweise durch PD weiter gefördert. Die Dauer, wie lange PD durchgeführt werden kann, unterscheidet sich bei Zystennieren-Patienten nicht von der Therapiedauer bei Patienten mit nicht-zystischen Nierenerkrankungen. Zystennieren-Patienten mit abdominellen Beschwerden wie Meteorismus, Völlegefühl oder Kreuzschmerzen verursacht durch die Organvergrößerung sollte nicht unbedingt aktiv zur Peritonealdialyse geraten werden, da die Symptome durch die PD weiter verstärkt werden können. Gleiches gilt für Patienten mit rezidivierenden Hernien. Allen anderen Zystennierenpatienten sollte aber sehr wohl die Methode zur Wahl vorgestellt werden, zumal Techniküberleben, Dialysequalität oder methodenspezifische Komplikationsraten mit jenen bei Patienten mit nicht-zystischen Nierenerkrankungen vergleichbar sind. PD stellt auch für Patienten mit Polyzystischer Nierendegeneration eine gleichwertige Behandlungsalternative zur Hämodialyse dar.

Diabetische Nephropathie – Update 2012

SummaryDiabetes mellitus is the leading single cause for renal replacement therapy. Its development and progression, however, can be ameliorated by adequate therapy. The present article represents the recommendations of the Austrian Diabetes Association and the Austrian Society for Nephrology for the prevention and treatment of diabetic nephropathy.ZusammenfassungDiabetische Nephropathie ist die führende Ursache der Nierenersatztherapie und die häufigste Nierenkrankheit geworden. Die Entwicklung und das Fortschreiten kann durch optimierte Therapie beeinflusst werden. Im vorliegenden Artikel werden die gemeinsamen Empfehlungen der Österreichischen Diabetesgesellschaft und der Österreichischen Gesellschaft für Nephrologie dargestellt.