Rituximab in adult patients with multi-relapsing/steroid-dependent minimal change disease and focal segmental glomerulosclerosis: a report of 5 cases.

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are common causes of nephrotic syndrome in children and adults. However, frequent relapses, steroid dependence, steroid resistance, and side effects of immunosuppressive therapy remain a therapeutic challenge. Rituximab (RTX) has evolved as an efficacious alternative in childhood MCD/FSGS. We report the effect of RTX in 5 adult patients with multirelapsing/steroid-dependent nephrotic syndrome due to MCD or FSGS. RESULTS: All five patients treated with RTX achieved sustained complete remission and additional immunosuppression was withdrawn. One patient had a relapse after 23 months, which was successfully treated with a further series of RTX infusion without reinitiation of steroid therapy. Serious adverse events related to RTX therapy were not observed in our patients. CONCLUSIONS: Our results indicate that RTX is effective and cessation of additional immunosuppressants could be achieved in all patients reported in this study. RTX may be an effective alternative therapy in adult patients with multirelapsing/steroid-dependent nephrotic syndrome due to MCD or FSGS.

Patients with adult minimal change nephrotic syndrome treated with long-term cyclosporine did not experience a reduction in their eGFR.

BACKGROUND: The long-term efficacy and safety of cyclosporine (CyA) in the treatment of adult minimal change nephrotic syndrome (MCNS) was examined. METHODS: The medical record of 15 patients diagnosed with MCNS by renal biopsy and treated with CyA for at least 2 years were reviewed. RESULTS: The mean administration period of CyA was 78.3 months. The mean CyA dose for the induction period was 2.1 ± 0.9 mg/kg and 1.7 ± 1.0 mg/kg for the maintenance period. The mean dose of prednisolone used during the induction period was 20.3 mg and 2.7 mg during the maintenance. The frequency of MCNS relapse was decreased to 0.5 times/year in patients treated with CyA, compared to treatment without CyA (2.4 times/y). Two cases of mild liver damage and 3 cases of elevated blood pressure were observed during the administration of CyA. These adverse effects improved after reducing the CyA dose or treatment with an antihypertensive agent. A decrease in the estimated glomerular filtraion rate (eGFR) was not associated with long-term CyA use. CONCLUSION: At our institution, patients who were treated for MCNS with CyA for at least 2 years experienced no deterioration in renal function.

Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteria-poliomyelitis-vaccination.

BACKGROUND: The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS). In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. CASE PRESENTATION: A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l). About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. CONCLUSION: Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.

Combined therapy of cilazapril and losartan has no additive effects in ameliorating adriamycin-induced glomerulopathy.

AIMS: Effects of the blockade of renin-angiotensin system (RAS), by angiotensin-converting enzyme inhibitor (ACEi), type 1 angiotensin II receptor blocker (ARB), or a combination of both, were evaluated in Adriamycin (ADR)-induced glomerulopathy. METHODS: Male Sprague-Dawley rats (180-250 g) were induced of glomerulopathy by treatment with ADR (2 mg/kg, i.v.). Six weeks later, they were treated with cilazapril (1 mg/kg/day) and/or losartan (10 mg/kg/day) for an additional 6 weeks. RESULTS: The urinary excretion of protein progressively increased following the treatment with ADR, which was prevented by ACEi, ARB, and a combination of both. Similarly, the glomerulopathy assessed by glomerulosclerosis index was also ameliorated by ACEi or ARB. However, combined therapy of both ACEi and ARB was without an additional effect (Control 1.4 +/- 0.4%, ADR 10.7 +/- 2.7%**, ACEi 0.8 +/- 0.4%, ARB 2.6 +/- 1.0%, ACEi+ARB 1.7 +/- 1.5%, ** p < 0.01 vs. Control). The expression of transforming growth factor-beta(1) was increased following the treatment with ADR (1.4 +/- 0.07-fold, p < 0.05 vs. Control), however, the degree of which was similarly blunted by either ACEi, ARB, or the combination of both. The expression of type 1 angiotensin II receptor mRNA increased following the treatment with ADR, the degree of which was further upregulated by ACEi and decreased by ARB to the control level (ADR 1.3 +/- 0.06-fold*, ACEi 1.8 +/- 0.05-fold***, ARB 1.0 +/- 0.04-fold, * p < 0.05 and *** p < 0.001 vs. Control). The combined therapy of ACEi and ARB still showed an upregulation of type 1 angiotensin II receptor mRNA, however, of which degree was mitigated compared with that induced by ACEi alone (ACEi+ARB 1.5 +/- 0.04-fold, ** p < 0.01 vs. Control). On the contrary, the expression of type 2 angiotensin II receptor mRNA was downregulated following the treatment with ADR, which was similarly restored to the control level by ACEi, ARB, and a combination of both (ADR 0.5 +/- 0.08-fold**, ACEi 1.0 +/- 0.06-fold, ARB 1.0 +/- 0.05-fold, ACEi+ARB 1.0 +/- 0.05-fold, ** p < 0.01 vs. Control). CONCLUSION: It is suggested that combined therapy of ACEi and ARB with relatively high or maximal doses of each drug has no additive or synergistic benefits on the progression of ADR-induced glomerulopathy. Effects of RAS blockade may in part be related to differential regulation of type 1 and type 2 angiotensin II receptors.

Minimal change nephrotic syndrome with cecum adenocarcinoma.

Membranous glomerulonephritis is the most common glomerular disease associated with malignancy, the association of minimal change glomerulopathy with solid tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due to minimal change glomerular disease; an accurate seek of underlying malignancy revealed a cecum adenocarcinoma. We had a complete remission of nephrotic syndrome after surgery of carcinoma.

Cholestyramine resin ameliorates chronic aminonucleoside nephrosis.

We chose to assess the role of cholesterol reduction in chronic aminonucleoside nephrosis by pharmacologically lowering serum cholesterol with cholestyramine. Two groups of rats were made nephrotic with a single intravenous dose of puromycin aminonucleoside (PA): one group (PA/resin) received 5% (w:w in diet) cholestyramine resin and the dietary control group (PA/cell) received 5% cellulose. Cholestyramine-treated rats demonstrated significant functional and histological protection. Recurrent proteinuria was significantly lower in PA/resin animals. Whole-kidney glomerular filtration rate in the PA/resin group was preserved at a level equivalent to normal age-matched control rats whereas the PA/cell group had a significantly lower value than did the normal animals. The extent of segmental glomerulosclerosis 24 wk after PA delivery was significantly lower in the PA/resin group. These results suggest a role for hyperlipidemia as one of the mechanisms involved in the pathogenesis of progressive glomerular disease.

A comparison between islet transplantation and parenteral insulin in the control of diabetes and prevention of renal complications in mice.

The control of diabetes and the prevention of renal complications were studied in mice that received different treatment regimes for six months. Transplantation of syngeneic cultured fetal pancreas completely reversed streptozotocin-induced diabetes (mean FBG 5.1 +/- 0.4 mmole/liter six months after transplantation, versus 5.8 +/- 0.2 mmole/liter in normal mice). The mean fasting blood glucose (FBG) level of insulin-treated mice was lower than the mean FBG level of untreated diabetic mice (9.0 +/- 1.2 mmole/liter versus 11.5 +/- 1.3 mmole/liter, P less than 0.05) but exceeded the FBG level of transplanted mice (P less than 0.001) or normal controls (P less than 0.001). There were no significant differences between the mean level of glycosylated hemoglobin (HbA1c) of normal (4.8 +/- 0.3%), transplanted (4.5 +/- 0.3%), or insulin-treated mice (5.3 +/- 0.4%), but the HbA1c level in the untreated diabetic group was increased (7.0 +/- 0.5%; P less than 0.001). Six months after transplantation, the thickness of the glomerular capillary basement membrane (GCBM) was not different in the transplanted group and normal controls (156.4 +/- 5.7 nm versus 157.3 +/- 12.6 nm); the GCBM was thicker in the insulin-treated mice than in the transplanted mice (179.8 +/- 4.2 nm versus 156.4 +/- 5.7 nm; P less than 0.02), but thinner than in untreated diabetic mice (179.8 +/- 4.2 nm versus 202.2 +/- 4.4 nm; P less than 0.001). It is concluded that islet transplantation, in contrast to good control as judged by normalization of HbA1c levels achieved with parenteral insulin, prevents GCBM thickening in experimental diabetes.