Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5-5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high-dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non-randomized trials. Differentiated, precise, larger, randomized, placebo-controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN.

Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long-term follow-up.

In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long-term follow-up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP-MPA). In a median observation time of 6·2 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy-proven IgAN and treated with CyP. Thirty-one patients with further progression were treated with MPA maintenance for a median time of 5·2 years. Follow-up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 0·9 ml/min to 0·1 ml/min per month with CyP (P < 0·05), and with MPA in patients with a relapse from -0·4 ml/min to -0·1 ml/min per month (P < 0·05) until the end of the study. Proteinuria decreased significantly from 1·6 g/l to 1·0 g/l after CyP, and during MPA treatment to 0·6 g/l (P = 0·001 Friedman test). Median renal survival time was in patients with CyP 10·5 years (range = 3·2-17·8), with CyP-MPA 10·7 years (range = 8·3-13·1), with IVIg 4·7 years (range = 2·6-6·6), and in untreated patients 1·2 years (range = 0·8-1·6; log-rank test P < 0·01). In patients with progressive IgAN, our long-term follow-up observation indicates that sequential CyP-MPA therapy maintains renal survival significantly.

[Pattern laser trabeculoplasty and argon laser trabeculoplasty for treatment of glaucoma]. / Pattern-Laser-Trabekuloplastik und Argon-Laser-Trabekuloplastik zur Glaukombehandlung.

INTRODUCTION: Argon laser trabeculoplasty (ALT) and pattern laser trabeculoplasty (PLT) are two laser surgery methods for treatment of open angle glaucoma and the effect in reducing intraocular pressure (IOP) of these methods was compared in a retrospective study. METHODS: The IOP, the best corrected visual acuity (BCVA) and the eye drop glaucoma medication used by patients who were treated by ALT or PLT in this clinic between January 2011 and December 2012 were compiled and evaluated. RESULTS: An ALT was carried out on 22 eyes from 22 patients (13 right and 9 left eyes in patients with an average age of 71.1 ± 1.5 years, 7 men and 15 women) and a significant average reduction of IOP from 18.6 ± 0.9 to 15.3 ± 0.7 mmHg (p < 0.001) was observed an average of 8.2 ± 0.8 weeks after ALT. The number of dropped glaucoma medications per eye (p = 0.19) and the mean BCVA both remained constant (p = 0.15). A PLT was carried out on 20 eyes from 20 patients (12 right and 8 left eyes in patients with an average age of 69.9 ± 2.6 years, 10 men and 10 women) and a significant average reduction of IOP from 20.2 ± 1.1 to 15.6 ± 0.8 mmHg (p < 0.001) was observed an average of 8.3 ± 0.6 weeks after PLT. The number of dropped glaucoma medications per eye (p = 0.08) and the mean BCVA both remained constant (p = 0.59). The difference in the reduction of IOP between the ALT and PLT groups was not significant (p=0.26). CONCLUSION: Both PLT and ALT are effective methods for treatment of open angle glaucoma and lead to similar significant reductions in IOP.

Responses of subjects with spinal cord injuries to maximal wheelchair exercise: comparison of discontinuous and continuous protocols.

Six male subjects with spinal cord injuries (SCI) participated in this investigation to compare peak values of oxygen uptake (VO2), heart rate (fc), ventilation (VE), respiratory exchange ratio (R) and power output (W) obtained using a discontinuous (DP) and a continuous jump max protocol (JMP) in a maximal wheelchair exercise test on a treadmill. The W increments were achieved by imposing an extra mass upon the wheelchair through a pulley system. The DP involved exercise periods of 3 min separated by 2-min intervals at relative rest. Increments in W consisted of 0.10 or 0.15 W.kg-1 total mass. During the rest intervals no mass was imposed on the wheelchair. The JMP involved an increase in W each minute. Increments and velocity in the JMP were the same as during the exercise periods for DP. Mean peak values for W [99.5 (SD 13.6) W], VO2 [2.13 (SD 0.27) l.min-1, standard temperature and pressure, dry], R [1.25 (SD 0.16)] and VE [82.8 (SD 11.2) l.min-1, body temperature and pressure, saturated] in DP were not different from values observed for W [103.5 (SD 13.1)], VO2 [2.18 (SD 0.31) l.min-1], R [1.17 (SD 0.16)] and VE [78.9 (SD 16.0) l.min-1] in the JMP. The only significant difference was observed for fc: 198 (SD 11) beats.min-1 in DP and 187 (SD 11) beats.min-1 in JMP. The higher values for fc elicited using DP have been discussed. It was concluded that both a DP and a JMP seem to be equally appropriate in determining peak VO2 and peak W in SCI persons.(ABSTRACT TRUNCATED AT 250 WORDS)