Biosimilar epoetin zeta in nephrology - a single-dialysis center experience.

AIM: An observational clinical study was performed to test the efficiency of the biosimilar product epoetin zeta to maintain stable hemoglobin levels in end-stage renal disease (ESRD) patients on intermittent high-flux hemodialysis. PATIENTS AND METHODS: Before the start of the study, 17 out of 18 patients were on various erythropoiesis-stimulating agents (ESA). After a run-in period of 2 months, all patients switched to epoetin zeta and were followed for 6 months. The initial weekly doses as well as the frequency of application per week were kept constant. To convert patients on darbepoetin (n = 12) to epoetin zeta, a factor of 1 : 200 was used. During the follow-up, hemoglobin levels, iron status, dialysis efficiency, body weight, and adverse events were monitored at least once a month. RESULTS: Comparing time 0 (before the start of epoetin zeta) with the end of the study (6 months of epoetin zeta), no significant changes were observed: Hemoglobin 11.72 ± 0.64 g/dl versus 11.62 ± 0.70 g/dl (p = 0.64); weekly dose of ESA: 79.4 ± 57.7 IU/kg/week at start versus 91.8 ± 65.4 IU/kg/week at the end (p = 0.55). It is noteworthy that the frequency of application could be reduced to once a week or less with epoetin zeta in 66% of the 18 patients. After 6 months of epoetin zeta, 10 patients received 1 dose/week, and 2 patients received only 1 dose every 2 weeks. There were no significant changes in mean blood pressure, body weight and hemodialysis efficiency comparing the end with the start of the observation. No side effects attributable to the ESA-therapy have been observed. CONCLUSION: The biosimilar product epoetin zeta is safe in clinical practice and is effective and stable in the weekly dose as well as in the frequency of application. Biosimilars offer a welcome opportunity to reduce treatment costs of renal anemia.

Predicting outcome and survival in patients with Wegener's granulomatosis treated on the intensive care unit.

OBJECTIVE: This study was designed to search for risk factors predicting mortality of patients with Wegener's granulomatosis (WG) treated on the intensive care unit (ICU). METHODS: Seventeen patients admitted to the ICU of an University Hospital for an acute illness related to WG were analysed retrospectively over 4 years. A variety of clinical and laboratory variables were recorded. Contingency table analyses, univariate logistic regression, and discriminate analysis were performed to determine which factors influenced a negative outcome. RESULTS: Reasons for ICU admission were respiratory failure (n = 10), severe haemoptysis (n = 13), sepsis (n = 9), acute renal failure (n = 6), and gastrointestinal bleeding (n = 1). Patients were treated for a median of 6 days (range 4-121 days). During the stay in the ICU, five patients died within 24-121 days (overall mortality 29.4%). Causes of death were cerebral haemorrhage (n = 2), pulmonary embolism (n = 1), and sepsis (n = 2). Significantly associated with death were: Acute Physiology and Chronic Health Evaluation II (APACHE II) score>24 [p = 0.004, odds ratio (OR) 0.568, 95% confidence interval (CI) 0.327-0.989], period of time in the ICU>10 days (p = 0.001, OR 0.795, 95% CI 0.589-1.072), and treatment with cyclophosphamide during the stay in the ICU (p = 0.013, OR 0.799, 95% CI 0.651-0.980). No association was found for higher age, C-reactive protein (CRP), pulmonary involvement, serum creatinine, and requirement of haemodialysis. CONCLUSIONS: The prognosis for WG patients in the ICU is serious, but the majority can survive. To achieve a more favourable outcome, patients should stay in the ICU for as short a time as possible. The occurrence of renal failure did not influence the outcome in our patients.

[Diagnostics and therapy of diabetic nephrology]. / Diagnostik und Therapie der diabetischen Nephropathie.

In Germany, 36% of all new chronic dialysis patients have diabetic nephropathy. The majority are type 2 diabetics. Early intervention has the greatest effect. Incipient nephropathy can be diagnosed by evidence of microalbuminuria (30-300 mg albumin/g creatinine). Proteinuria on the standard test strip (>300 mg/g) indicates manifest nephropathy followed by progressive renal failure. Important cofactors for progression are hypertension, hyperglycemia, and smoking. Low normal blood pressure levels (<130/80 mmHg without and <125/75 mmHG with proteinuria) based on ACE inhibitors/AT1 blockers are the goal. Combination therapies are frequently necessary. This can often reverse microalbuminuria. Chronic renal failure requires special attention (e.g. bone metabolism, anemia, acidosis). Timely initiation of renal replacement therapy (GFR <15 ml/min) reduces morbidity and mortality. In addition to hemo- and peritoneal dialysis, early kidney and in individual cases of type 1 diabetes combined kidney/pancreas transplantation is appropriate.

Automated peritoneal dialysis with 'on-line'-prepared bicarbonate-buffered dialysate: technique and first clinical experiences.

BACKGROUND: Automated peritoneal dialysis (APD) has the possibility of increasing the dialysis efficacy by using higher fill volumes, frequent dialysate exchanges, and tidal techniques. It is then possible to treat patients adequately without residual renal function. The drawbacks of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of lactate-based dialysate bags and difficulties for the patients in handling these bags. So far, bicarbonate-based peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line preparation of substitution fluid for haemofiltration. METHODS: Four patients without residual renal function were treated with APD five times weekly in a crossover study design. Patients received standard lactate-based (35 mmol/l) treatment (25 litres per session each) in weeks 1 and 3. In week 2 on-line-produced bicarbonate-buffered (37 mmol/l) dialysate was used. This dialysate was prepared by an AK 100 Ultra haemodialysis machine. The machine was modified for adding glucose from a 50% concentrate to the desired concentration of 1.7%. Electrolytes, pH, pCO2, and dialysis efficacy parameters were measured. Microbiological testing was carefully performed. RESULTS: Creatinine clearances, Kt/V, and pCO2 did not vary between the different treatment phases, whereas the pH showed a distinct increase during the bicarbonate phase. Repeated determinations of endotoxins and culturing showed no contamination of the dialysate. The composition of the produced dialysate was reproducible with respect to pH, pCO2, sodium, calcium and bicarbonate, whereas the glucose concentration varied by +/- 20%. CONCLUSIONS: On-line preparation of PD fluid with the AK 100 Ultra is easy and safe to handle. APD with dialysate containing 37 mmol/l bicarbonate provides improved acid base balance and possibly improved biocompatibility, and may lead to a significant cost reduction. Further development in order to provide smaller machines and more precise ways of achieving a desired dialysate glucose concentration is necessary.

Peritoneal mononuclear cell differentiation and cytokine production in intermittent and continuous automated peritoneal dialysis.

The long period without dialysate exchanges in nightly intermittent peritoneal dialysis (NIPD; no peritoneal filling during the day) and continuous cyclic peritoneal dialysis (CCPD; peritoneal filling during the day) might lead to an improved repopulation and functional regeneration of peritoneal macrophages (PMOs). We investigated this issue in seven stable, noninfected CCPD patients and seven stable, noninfected NIPD patients. PMO differentiation and cytokine production were measured after automated peritoneal dialysis and after a 12- to 14-hour period without dialysate exchanges. PMO maturation was evaluated by antibody staining. The proportion of "young" monocytes (positive for 27E10 and RM3/1) was decreased, whereas the proportion of mature macrophages (positive for 25F9) was significantly increased after the exchange-free interval. No differences between NIPD and CCPD were observed. The cytokine response to lipopolysaccharide was significantly increased after the exchange-free interval in both NIPD and CCPD. The interleukin-1 receptor antagonist (IL-1Ra) content of PMO lysates significantly increased after the exchange-free interval in both groups, but no changes were found in dialysate and serum IL-1Ra. We conclude that the long daytime interval without dialysate exchanges allows for additional PMO differentiation. Furthermore, the potential for cytokine release, which is inhibited (possibly by dialysate effects) after automated peritoneal dialysis, is restored after a 12- to 14-hour interval without peritoneal dialysis exchanges. The "dry" day in NIPD seems to have no important additional positive effect compared with CCPD.

Single-center experience with renal transplantation in patients with Wegener's granulomatosis.

Between 1980 and 1995, 13 patients with end-stage renal disease due to Wegener's granulomatosis received 14 renal transplants (10 cadaveric, 4 living related). The mean follow-up in the 13 successfully transplanted patients was 50 months (4-107 months). One patient had primary nonfunction and received another graft 4 months later. Three episodes of acute rejection occurred in two patients, and one of these patients lost her graft due to severe vascular rejection 4 months after transplantation. Two patients died with well-functioning grafts (one of metastatic cancer and one of sepsis). One patient presented with perisinusitis and had a mild recurrence of Wegener's disease. None of the patients developed recurrent disease in the transplanted organ. At the last follow-up, the mean creatinine (+/-SD) in the 12 patients with functioning grafts was 1.6 +/- 0.6 mgdl. We conclude that renal transplantation is an excellent treatment for renal failure due to Wegener's granulomatosis. Recurrence of the disease is uncommon in patients under immunosuppression, but careful monitoring is extremely important.

Urodilatin is involved in sodium homeostasis and exerts sodium-state-dependent natriuretic and diuretic effects.

Urodilatin is involved in sodium homeostasis exerts sodium-state-dependent natriuretic and diuretic cts. Eight male volunteers participated in a study consisting of three consecutive phases of 7 days each. The volunteers a sodium diet with 52, 172.6, and 347.8 mmol um/day. Sodium excretion increased from 57.4 +/- 3.7 via .8 +/- 4.6 (P < 0.001) to 322.5 +/- 10.2 mmol/24 h (P < 0.001) at the end of each sodium diet. Urinary urodilatin excretion increased from 24.8 +/- 3.0 via 35.5 +/- 9.0 (P = 0.07) to 49.0 = mol/min (P < 0.01). At the end of each diet, urodilatin was infused for 2 h at 20 ng.kg body wt-1.min-1. Natriuresis increased after low- (4.1 to 52.9 mmol/h, P < 0.001), normal (6.9 to 44.9 mmol/h, P < 0.05), and high-sodium diet (20.1 to 102.9 mmol/h, P < 0.001). Diuresis increased from 174 to 709 (P < 0.001), 395 to 1,026 (P < 0.05), and 266 to 1,339 ml/h < 0.001). The present results indicate that endogenous urodilatin plays an important role in sodium homeostasis and that renal response to exogenous urodilatin is modulated by sodium balance.

Chronic induction of C-reactive protein by hemodialysis, but not by peritoneal dialysis therapy.

OBJECTIVE: Evaluation of the inflammatory activity in patients on chronic peritoneal dialysis (PD) and patients on chronic hemodialysis (HD) in comparison to patients with chronic renal insufficiency without dialysis treatment and healthy volunteers. DESIGN: Open, nonrandomized prospective study. SETTING: Nephrology Department, including HD and PD therapy in a university hospital. PATIENTS: Twenty-four patients on chronic PD,21 patients on chronic HD therapy using a cuprophan dialyzer,16 patients with chronic renal insufficiency without dialysis treatment, and 33 healthy volunteers; 8 additional patients before and after initiation of chronic HD therapy. All patients and controls were without infection or immunosuppressive therapy. MAIN OUTCOME MEASURES: As a marker of the inflammatory activity in the different patient groups, C-reactive protein (CRP) was measured serially using a sensitive, enzyme-linked, immunosorbent assay in order to detect values below the detection limit of standard assays. RESULTS: Patient groups had CRP levels higher than the normal controls (p < 0.01). Patients on HD had CRP levels significantly higher than PD patients (p < 0.01) whose levels were comparable to patients without dialysis therapy. Accordingly, longitudinal measurements before and after initiation of chronic HD showed a significant increase in CRP levels after the beginning of HD treatment (p < 0.04). CONCLUSIONS: The results suggest that induction of the inflammatory activity is lower during PD compared to HD, since stimulation by the dialyzer membrane, dialysate buffer, or bacterial fragments in the dialysate is avoided. This observation might indicate a possible lower risk of long-term complications in patients with PD.

Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis.

Because of the high rate of spontaneous remission, treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial. The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen. Seventeen patients with more than 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mumol/l) were included. Serum total protein, serum lipids, proteinuria, serum creatinine, and blood pressure were measured, along with the diuretic and antihypertensive medication. The observation time before the start of treatment was 27 +/- 27 months. Steroids were given during months 1, 3, and 5 (methylprednisolone 3 x 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month). Chlorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kgBW daily. At the end of treatment proteinuria had significantly decreased (mean of all patients, 7.8 +/- 1.4 g/d) in all patients. Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia had improved; diuretic and antihypertensive medication were reduced. Elevated serum creatinine decreased in 7 of 9 patients (pretreatment, 227 +/- 39 mumol/l; 6 months, 176 +/- 28 mumol/l). Nonresponders with respect to serum creatinine responded with respect to proteinuria. Regarding adverse effects, two patients complained of dyspepsia while taking steroids; during chlorambucil treatment two patients experienced nausea and lack of appetite, and one developed leukopenia (1600/microliters).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal effects of atrial natriuretic peptide in cirrhotic rats with and without captopril pretreatment.

Compared to healthy humans in most patients with cirrhosis and renal sodium and water retention, effects of atrial natriuretic peptide (ANP) on sodium and water excretion are reduced. It has been postulated that this impaired response to ANP is caused by renal vasoconstriction, induced by high levels of angiotensin II. To further investigate this issue, we studied renal hemodynamics (glomerular filtration rate, GFR, single nephron GFR, SNGFR, renal blood flow, RBF) and urinary sodium excretion (UNaV) in rats with CCl4-induced cirrhosis of the liver, before and during ANP infusion. The same parameters were determined in cirrhotic rats after a 4-day pretreatment with the angiotensin-converting enzyme (ACE) inhibitor captopril before and during ANP. Results were compared to those obtained in 2 control groups of healthy rats, one of them pretreated with captopril. Rats with cirrhosis had a significantly reduced GFR, SNGFR, RBF, UNaV and an elevated plasma renin activity compared to healthy controls. ANP caused a significant rise in UNaV (+198%) but no significant change of GFR, SNGFR and RBF in cirrhotic rats. Captopril-pretreated rats with cirrhosis had a significantly higher RBF (+26%) and 24-hour urinary sodium excretion (+52%) but no significant differences in GFR and SNGFR compared to cirrhotic rats without captopril pretreatment. Administration of ANP to cirrhotic rats pretreated with captopril resulted in a significant rise in GFR (+56%), SNGFR (+42%), RBF (+29%) and UNaV (+159%) compared to cirrhotic rats with ANP alone. In healthy rats, there was no additional effect of a combined therapy with captopril and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical experiences with nocturnal intermittent peritoneal dialysis]. / Klinische Erfahrungen mit der nächtlichen intermittierenden Peritonealdialyse.

Nocturnal intermittent peritoneal dialysis (NIPD) was performed in 56 patients (37 men, 19 women; mean age 44 [18-77] years, 18 of them diabetics). The NIPD protocol laid down 6-10 automatic changes of 1.5-2.3 1 dialysate (mean glucose concentration: 1.9%) each night. Clinical and biochemical tests were performed three times, at least 4 weeks apart (the first one after 2 months of stable NIPD). 36 of the 52 patients under the age of 60 were working. Mean hospital stay (excluding catheter implantation and training) was 5 days yearly. Mean peritonitis rate was one episode every 54 months. Because of technical problems a change from peritoneal to haemodialysis became necessary in four patients. Clinical and biochemical findings were: creatinine 877 +/- 269 mumol/l, urea 20 +/- 5.2 mmol/l, potassium 4.5 +/- 0.6 mmol/l, calcium 2.3 +/- 0.2 mmol/l, phosphate 1.7 +/- 0.5 mmol/l, total protein 69 +/- 7 g/l, cholesterol 6.8 +/- 1.7 mmol/l, and triglycerides 2.6 +/- 1.4 mmol/l. These data show that NIPD is an effective method of dialysis which--in comparison with other techniques--has several advantages. Peritonitis and technical failure are rare.

[Effect of captopril therapy on sodium and water excretion in patients with liver cirrhosis and ascites]. / Effekte einer Captopriltherapie auf die Natrium- und Wasserausscheidung bei Patienten mit Leberzirrhose und Aszites.

UNLABELLED: Ascites in patients with cirrhosis of the liver frequently is refractory to diuretic treatment. It was postulated that vasoconstriction of the renal cortex, mediated by activation of the renin-angiotensin-aldosterone-system (RAAS), may be one course of the disturbed sodium- and water-excretion in these patients. We therefore investigated in 14 cirrhotic patients with ascites under constant diuretic treatment the effects of low-dose captopril therapy on urinary sodium- and potassium-excretion, body weight, abdominal girth, serum-sodium, -potassium, creatinine-clearance, plasma-renin-activity (PRA), plasma-aldosterone (PA) and mean arterial pressure (MAP). After a control period of 4 days the patients received 2 x 6.25 mg/d captopril for 5 days and 4 x 6.25 mg/d for further 5 days. Treatment was followed by a second control period without captopril. PRA increased significantly after 2 days of captopril treatment. 2 x 6.25 mg/d captopril induced a significant increase in sodium excretion and a significant decrease of body weight. MAP decreased slightly but significantly without clinical signs of hypotension. 4 x 6.25 mg/d captopril resulted in a further reduction of body weight and a further enhancement of sodium excretion. Three days after withdrawal of captopril sodium output was significantly reduced again. CONCLUSION: In cirrhotic patients low-dose captopril seems to be efficient in the treatment of ascites resistant to diuretics without causing major side effects.