Casper F. M. Franssen

The incidence of primary glomerulonephritis worldwide: a systematic review of the literature

BACKGROUND Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries. METHODS All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. RESULTS This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100,000/year for membrano-proliferative GN, 0.2/100,000/year for mesangio-proliferative GN, 0.6/100,000/year for minimal change disease, 0.8/100,000/year for focal segmental glomerulosclerosis, 1.2/100,000/year for membranous nephropathy and 2.5/100,000/year for IgA nephropathy. Rates were lower in children at around 0.1/100,000/year with the exception of minimal change disease where incidence was reported to be 2.0/100,000/year in Caucasian children with higher rates in Arabian children (9.2/100,000/year) and Asian children (6.2-15.6/100,000/year). CONCLUSIONS This study found that incidence rates of primary GN vary between 0.2/100,000/year and 2.5/100,000/year. The incidence of IgA nephropathy is at least 2.5/100,000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found.

Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity : distinct differences between patients with anti-proteinase 3 and anti-myeloperoxidase autoantibodies

Franssen C, Gans R, Kallenberg C, Hageluken C, Hoorntje S (University Hospital, Groningen; Free University Hospital, Amsterdam; and Catharina Hospital, Eindhoven; the Netherlands). Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with antiproteinase 3 and antimyeloperoxidase autoantibodies. J Intern Med 1998; 244: 209–16.

Haemodialysis is associated with a pronounced fall in myocardial perfusion

BACKGROUND Whereas haemodialysis (HD) is lifesaving by replacement of renal function, there are data to suggest that the HD procedure itself may contribute to the high cardiac risk in dialysis patients. The HD procedure is associated with an increased risk of sudden death, and there is accumulating evidence that HD can elicit myocardial ischaemia. In this study, we evaluated the effect of HD on global and regional myocardial blood flow (MBF) and left ventricular (LV) function in non-diabetic, non-cardiac compromised patients. METHODS (13)N-NH(3) positron emission tomography (PET) was used to quantify changes in MBF, LV wall motion, cardiac output (CO), LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in seven non-diabetic patients with uneventful cardiac histories. PET scans were performed before and at 30 and 220 min of HD. RESULTS In all patients global MBF fell during HD. At 30 min of HD without ultrafiltration (UF), global MBF had fallen 13.5 +/- 11.5% (P < 0.05) while CO, LVEDV and LVESV were 4.6 +/- 5.3% (NS), 5.6 +/- 4.2% (P < 0.05) and 6.9 +/- 7.2% (P < 0.05) lower, respectively. At 220 min of HD, after UF of 2.5 +/- 0.9 l, global MBF had fallen 26.6 +/- 13.9% (P < 0.05) from baseline while CO, LVEDV and LVESV were 21.0 +/- 19.7%, 31.1 +/- 12.7% and 36.4 +/- 17.5% (all P < 0.05) lower, respectively. In two patients, new LV regional wall motion abnormalities (RWMA) developed at 220 min of HD. MBF was reduced to a greater extent in regions that developed LV RWMA compared to those that did not. CONCLUSIONS Haemodialysis induced a pronounced fall in MBF. Since MBF fell already early during HD not only hypovolaemia but also acute dialysis-associated factors seem to play a role. Haemodialysis-associated reductions in MBF may contribute to the high cardiac event rate of dialysis patients.

Hemodialysis-Induced Regional Left Ventricular Systolic Dysfunction: Prevalence, Patient and Dialysis Treatment-Related Factors, and Prognostic Significance

BACKGROUND AND OBJECTIVES The hemodialysis procedure may acutely induce regional left ventricular systolic dysfunction. This study evaluated the prevalence, time course, and associated patient- and dialysis-related factors of this entity and its association with outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Hemodialysis patients (105) on a three times per week dialysis schedule were studied between March of 2009 and March of 2010. Echocardiography was performed before dialysis, at 60 and 180 minutes intradialysis, and at 30 minutes postdialysis. Hemodialysis-induced regional left ventricular systolic dysfunction was defined as an increase in wall motion score in more than or equal to two segments. RESULTS Hemodialysis-induced regional left ventricular systolic dysfunction occurred in 29 (27%) patients; 17 patients developed regional left ventricular systolic dysfunction 60 minutes after onset of dialysis. Patients with hemodialysis-induced left ventricular systolic dysfunction were more often male, had higher left ventricular mass index, and had worse predialysis left ventricular systolic function (left ventricular ejection fraction). The course of blood volume, BP, heart rate, electrolytes, and acid-base parameters during dialysis did not differ significantly between the two groups. Patients with hemodialysis-induced regional left ventricular systolic dysfunction had a significantly higher mortality after correction for age, sex, dialysis vintage, diabetes, cardiovascular history, ultrafiltration volume, left ventricular mass index, and predialysis wall motion score index. CONCLUSIONS Hemodialysis induces regional wall motion abnormalities in a significant proportion of patients, and these changes are independently associated with increased mortality. Hemodialysis-induced regional left ventricular systolic dysfunction occurs early during hemodialysis and is not related to changes in blood volume, electrolytes, and acid-base parameters.

Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease

Endothelial progenitor cells (EPC) contribute to repair and maintenance of the vascular system, but in patients with chronic kidney disease (CKD), the number and function of EPC may be affected by kidney dysfunction. We assessed numbers and the angiogenic function of EPC from patients with CKD in relation to disease progression. In a cross-sectional, prospective study, 50 patients with varying degrees of CKD, including 20 patients undergoing dialysis and 10 healthy controls, were included. Mononuclear cells were isolated, and circulating EPC were quantified by flow cytometry based on expression of CD14 and CD34. EPC were cultured on fibronectin-coated supramolecular films of oligocaprolactone under angiogenic conditions to determine their angiogenic capacity and future use in regenerative medicine. CKD patients had normal numbers of circulating CD14+ EPC but reduced numbers of circulating CD34+ EPC. Furthermore, EPC from patients with CKD displayed functional impairments, i.e., hampered adherence, reduced endothelial outgrowth potential, and reduced antithrombogenic function. These impairments were already observed at stage 1 CKD and became more apparent when CKD progressed. Dialysis treatment only partially ameliorated EPC impairments in patients with CKD. In conclusion, EPC number and function decrease with advancing CKD, which may hamper physiological vascular repair and can add to the increased risk for cardiovascular diseases observed in CKD patients.

Relative Blood Volume Changes Underestimate Total Blood Volume Changes during Hemodialysis

BACKGROUND Measurements of relative blood volume changes (DeltaRBV) during hemodialysis (HD) are based on hemoconcentration and assume uniform mixing of erythrocytes and plasma throughout the circulation. However, whole-body hematocrit (Ht) is lower than systemic Ht. During HD, a change in the ratio between whole-body to systemic Ht (F cell ratio) is likely to occur as a result of a net shift of low Ht blood from the microcirculation to the macrocirculation. Hence, DeltaRBV may differ significantly from total blood volume changes (DeltaTBV). Therefore, this study compared DeltaRBV and DeltaTBV during HD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Plasma and erythrocyte volumes were measured using (125)I- and (123)I-radioiodinated albumin and (51)Cr-labeled erythrocytes, respectively. After validation of the standardized method in two patients on a nondialysis day, seven patients completed the protocol during HD. (125)I-albumin and (51)Cr-labeled erythrocytes were administered 20 min before the start of HD. (123)I-albumin was administered at 160 min into the HD session to quantify and correct for (125)I-albumin leakage. DeltaRBV was measured continuously throughout HD. The F cell ratio was derived from whole-body and systemic Ht. RESULTS Total ultrafiltration volume was 2450 +/- 770 ml. TBV declined from 5905 +/- 824 to 4877 +/- 722 ml during HD. Thus, TBV declined 17.3 +/- 4.4%, whereas the RBV decline was only 8.2 +/- 3.7% (P = 0.001). The F cell ratio increased from 0.896 +/- 0.036 to 0.993 +/- 0.049 during HD (P = 0.002). CONCLUSIONS DeltaRBV significantly underestimates DeltaTBV during HD. The rise in F cell ratio strongly suggests that during HD, blood translocates from the microcirculation to the macrocirculation, probably as a cardiovascular compensatory mechanism in response to hypovolemia.

Vasopressin, Copeptin, and Renal Concentrating Capacity in Patients with Autosomal Dominant Polycystic Kidney Disease without Renal Impairment

BACKGROUND AND OBJECTIVES Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary renal disease, characterized by cyst formation in the kidneys leading to end stage kidney failure. It is clinically acknowledged that ADPKD patients have impaired urine concentrating capacity, but the mechanism behind this observation is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Fifteen ADPKD patients (estimated GFR ≥60 ml/min per 1.73 m(2)) and 15 age- and sex-matched healthy controls underwent a standard prolonged water deprivation test in which urine and plasma osmolality, vasopressin, and copeptin were measured. The effect of a synthetic vasopressin analog (desmopressin) injected at the moment of maximal urine concentrating capacity was also studied. RESULTS After 14 hours of water deprivation, ADPKD patients tended to have higher plasma osmolality (P=0.07) and significantly higher vasopressin and copeptin levels (both P<0.05), whereas urine osmolality was similar in ADPKD patients and controls (710 versus 742 mOsmol/kg; P=0.61). Maximal urine concentrating capacity was lower in ADPKD patients (758 versus 915 mOsmol/kg in controls; P<0.001). At maximal urine concentrating capacity, plasma osmolality, vasopressin, and copeptin levels were significantly higher in ADPKD patients. The median increase in urine osmolality after desmopressin administration in ADPKD patients was less than in healthy controls. CONCLUSIONS Already early in their disease, ADPKD patients have impaired maximal urine concentrating capacity brought out upon dehydration, with no evidence of impaired hypothalamic response. To maintain fluid balance, vasopressin concentration increases, which is hypothesized to play a role in ADPKD disease progression.

Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis

Automatic feedback systems have been designed to control relative blood volume changes during hemodialysis (HD) as hypovolemia plays a major role in the development of dialysis hypotension. Of these systems, one is based on the concept of blood volume tracking (BVT). BVT has been shown to improve intra‐HD hemodynamic stability. We first questioned whether BVT also improves post‐HD blood pressure stability in hypotension‐prone patients and second, whether BVT is effective in reducing the post‐HD weight as many hypotension‐prone patients are overhydrated because of an inability to reach dry weight. After a 3‐week period on standard HD, 12 hypotension‐prone patients were treated with two consecutive BVT treatment protocols. During the first BVT period of 3 weeks, the post‐HD target weight was kept identical compared with the standard HD period (BVT‐constant weight; BVT‐cw). During the second BVT period of 6 weeks, we gradually tried to lower the post‐HD target weight (BVT‐reduced weight; BVT‐rw). In the last week of each period, we studied intra‐HD and 24 hr post‐HD blood pressure behavior by ambulatory blood pressure measurement (ABPM). Pre‐ and post‐HD weight did not differ between standard HD and either BVT‐cw or BVT‐rw. Heart size on a standing pre‐dialysis chest X‐ray did not change significantly throughout the study. There were less episodes of dialysis hypotension during BVT compared with standard HD (both BVT periods: p<0.01). ABPM data were complete in 10 patients. During the first 16 hr post‐HD, systolic blood pressure was significantly higher with BVT in comparison with standard HD (both BVT periods: p<0.05). The use of BVT in hypotension‐prone patients is associated with higher systolic blood pressures for as long as 16 hr post‐HD. BVT was not effective in reducing the post‐HD target weight in this patient group.

Relative blood volume measurements during hemodialysis: Comparisons between three noninvasive devices

The monitoring of relative blood volume changes (ΔRBV) has been advocated for the prevention of hemodialysis (HD) hypotension. Stand‐alone devices (Crit‐Line) or devices incorporated into the HD apparatus (blood volume monitor [BVM], Hemoscan) are widely used for this purpose. Comparisons between devices are scarce. The aim of this study was, first, to compare ΔRBV results from these 3 devices with ΔRBV calculated from changes in laboratory‐derived hemoglobin (ΔRBV‐lab‐Hb) and, second, to compare ΔRBV results between the different devices. Fourteen patients received 2 HD treatments in a randomized order: one with the Hemoscan and Crit‐Line combination and one with the BVM and Crit‐Line combination. ΔRBV‐lab‐Hb was measured at 2 and 4 hr into the HD session. Bland‐Altman analyses showed that ΔRBV results from the 3 devices differed systematically from ΔRBV‐lab‐Hb, i.e., the difference between the 3 devices and ΔRBV‐lab‐Hb varied significantly (p<0.05) with the magnitude of the measurement. The interdevice comparison showed considerable differences in ΔRBV results. At the end of the treatment, a significant difference (p<0.05) between ΔRBV measured by the Hemoscan and Crit‐Line device (−9.8±2.7% and −11.5±4%, respectively) was found. In most patients, a systematic difference between Crit‐Line and Hemoscan and between Crit‐Line and BVM was observed. Relative blood volume change measurements by Crit‐Line, Hemoscan, and BVM yield results that differ systematically from the results obtained from laboratory‐derived Hb changes. Furthermore, there are substantial differences in ΔRBV results between the 3 ΔRBV devices.

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis.

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.