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Objective: Treatment with heparins and ACE-inhibitors lower proteinuria in diabetic nephropathy (DN). Besides its hemodynamic effects, angiotensin II inhibits synthesis of glomerular heparansulfatproteoglycans (HSPG). In vitro, heparins modulate angiotensin II (ANG II) signaling in cultured glomerular cells. It has also been described that heparins inhibit aldosteron synthesis. It is not known, if the in vivo effects of heparin on proteinuria are mediated via the RAAS.This study was performed to assess the influence of heparins on the RAAS in vivo by testing whether the antiproteinuric effects of heparins are mediated hemodynamically. Methods: 10 patients with diabetic nephropathy [D], 10 patients with non-diabetic nephropathy [ND] (IgA- or membranous GN) and 10 healthy controls [C] were examined before and after a 9 week period on low-dose enoxaparin 4000 IE s.c. per day. Renal and systemic hemodynamics were determined by infusion clearance technique with 99 mTc-DTPA and 131I-hippurate and with Dinamap. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), mean arterial pressure (MAP) and heart rate (HR) were measured on baseline and during ANG II infusion (8 mg/kg/min) twice before and twice after heparin treatment on normal salt diet and on salt restriction respectively. Results: In all groups, GFR remained stable before and after ANG II infusion. ANG II caused a consistent and significant decrease in ERPF and a consecutive increase in filtration fraction and renal vascular resistance, while MAP and HR increased significantly. Heparin treatment did not alter the ANG II-induced changes in renal and systemic hemodynamics neither on normal salt diet nor on salt restriction. All groups showed identical renal and systemic hemodynamic responses to ANG II before and after heparin therapy. Only in diabetics heparin treatment caused a significant decrease in proteinuria: on normal salt diet from 822 ± 793 to 476 ± 397 mg/24 h, p < 0.05 and after salt restriction from 600 ± 828 to 468 ± 669 mg/24 h, p < 0.05. Heparin therapy did not lower aldosterone levels. Conclusions: These findings show, that the antiproteinuric effect of heparin cannot be explained via interaction with the RAAS. The absence of hemodynamic changes together with a significant decrease in proteinuria can only be explained by intrinsic alterations in the glomerular filter after heparin therapy. The effects could only be demonstrated in ND, not in IgA or membranous glomerulonephritis. [ABSTRACT FROM AUTHOR]

Objective: A subset of patients with WG is refractory to treatment with cyclophosphamide (CYC) plus glucocorticosteroids (GC). A 6 months course of the immunosuppressant DSG has previously been successfully employed in refractory WG. However, there are no reports in the literature on long-term treatment with DSG. Methods: To document the effects of long-term DSG treatment this follow-up study of a previous pilot trial reports on 7 patients suffering of refractory WG, who were successfully treated with DSG over an average of 26.5 (range: 11-55.5) months. Results: Before administration of DSG, patients had received a mean of 5.4 (2-11) different therapeutic approaches including GC and CYC in all and experimental therapies in 4, without control of disease activity (6.6 [range: 3-12] relapses during a disease duration of 4.7 [1.5-9] years). Four patients were unresponsive to CYC, and 3 did not tolerate it. All six suffered of active WG when DSG treatment was initiated (mean Birmingham vasculitis activity score: 16.1 [4-25]). DSG (0.5 mg/kg/day s.c.) was given for 2 to 3 weeks until the WBC count dropped to 3,000/µl followed by a rest until a WBC of 4,000/µl was reached again. No other immunosuppressants besides steroids were given. All patients showed a long lasting, favorable response to DSG with partial (n = 2) or complete (n = 5) remission. Only one of the cases relapsed while being treated with DSG. Termination/interruption of DSG treatment in 3 cases was followed by relapse in 4 of 5 occasions. Resumption of DSG lead to complete remission. Currently, 5 of the 7 patients are still treated with DSG and are in remission. Infections, mainly of the respiratory tract, were observed in 5 cases and required hospitalisation in one. This case developed a 3rd degree heartblock that required pacing. Otherwise, infections resolved under adequate treatment without sequels. Conclusions: Long-term treatment with DSG seems safe and successful in patients with refractory WG under careful monitoring of WBC counts. [ABSTRACT FROM AUTHOR]

Abstract Background An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design. Methods We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed. Results The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 – 1.0) and 1.0 (0.8 – 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a significantly decreased risk, a tiny subgroup of extreme users with over 3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg lifetime use recommended by the regulatory advisors showed an impressive excess of other conditions than analgesics triggering the evolution of ESRD in cases compared with controls. Conclusion We found no clinically meaningful evidence for an increased risk of ESRD associated with use of phenacetin-free analgesics in single or combined formulation. The apparent risk increase shown in a small subgroup with extreme lifetime dose of analgesics is most likely an indirect, non-causal association. This hypothesis, however, cannot be confirmed or refuted within our case-control study. Overall, our results lend support to the mounting evidence that phenacetin-free analgesics do not induce ESRD and that the notion of "analgesic nephropathy" needs to be re-evaluated.

Abstract Background Methylene bis(thiocyanate) (MBT) is a microbiocidal agent mainly used in industrial water cooling systems and paper mills as an inhibitor of algae, fungi, and bacteria. Case presentation We describe the first case of severe intoxication following inhalation of powder in an industrial worker. Profound cyanosis and respiratory failure caused by severe methemoglobinemia developed within several minutes. Despite immediate admission to the intensive care unit, where mechanical ventilation and hemodialysis for toxin elimination were initiated, multi-organ failure involving liver, kidneys, and lungs developed. While liver failure was leading, the patient was successfully treated with the MARS (molecular adsorbent recirculating system) procedure. Conclusion Intoxication with MBT is a potentially life-threatening intoxication causing severe methemoglobinemia and multi-organ failure. Extracorporeal liver albumin dialysis (MARS) appears to be an effective treatment to allow recovery of hepatic function.

Abstract Background The association between intake of non-phenacetin-containing analgesics and the occurrence of chronic renal failure is still controversially discussed. A new epidemiologic study was planned and conducted in Germany and Austria. Methods/design The objective of the international, multicenter case-control study was to evaluate the association between end-stage renal disease (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis on combined formulations. A targeted sample of 1000 new (incident) dialysis patients, aged less than 50 years, was planned to recruit between January 1, 2001 and December 31, 2004. The age limit was chosen to avoid contamination of the study population with phenacetin-containing analgesics to the extent possible. Four control subjects per ESRD case, matched by age, sex, and region were selected from the population living in the region the case came from. Lifetime exposure to analgesics and potential renal risk factors were recorded in a single face-to-face interview. A set of aids was introduced to reinforce the memory of study participants. A standardized, pre-tested interview questionnaire (participants), a medical documentation sheet (physicians in dialysis centres), a logbook for all activities (dialysis centres) were used to collect the necessary data. Quality management consisted of the standardized procedures, (re-) training and supervision of interviewers, regular checks of all incoming data for completeness and plausibility. The study is scientifically independent and governed by a international Scientific Advisory Committee that bridged the gap between the sponsoring companies and the investigators. Also other advisory groups assisted the managing committee of the study. All relevant German and Austrian nephrological associations supported the study, and the study design was carefully reviewed and approved by the Kidney Foundation of Germany. Discussion The study is expected to answer the main research question by end 2005. There is however a high potential for various biases that we tried to address with adequate measure. One limitation however cannot be overcome: The methodologically needed age-limitation of the study will make it not easy to generalize the results to age groups over 50 years. It might be suggested to repeat the study for persons over 50 years in 10 years when contamination with phenacetin use early in life is likely to be outgrown.

The article discusses the case of a 47 year old woman with an exceptional severe iron deficiency anemia. She was hospitalized because of a hemoglobin level that had attracted attention when she was donating blood. At that time, she suffered fatigue and occasionally frontal headaches. This unusual case is related to long term ingestion of large amounts of purchasable crayons, which is similar to the diagnostic criteria of adult pica.