Plasmapheresis treatment for recurrent focal sclerosis in pediatric renal allografts

Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric renal allografts is associated with a poor graft survival. This study reports on plasmapheresis for the treatment of recurrent FSGS in pediatric renal transplant recipients. The records of 100 consecutive pediatric (age <21 years) renal transplants were reviewed. Twenty patients had FSGS as the cause of renal failure. Eight of these (40%) had a recurrence (protein-uria >1 g/m² per day) within 1 month of transplantation. Five of six patients treated with plasmapheresis went into remission (<0.2 g/m² per day), receiving a total of 42±26 (12–73) sessions, with the mean number of sessions required to achieve a remission being 24±17 (8–51). One patient had a second recurrence 1 year following cessation of plasmapheresis and responded to another course of plasmapheresis. The 1 patient who did not respond to plasmapheresis had a delay in initiation of therapy of 42 days. Plasmapheresis initiated within 48 h of recurrence resulted in earlier remissions and improved graft survival among our patients. Plasmapheresis appears to be effective in treating recurrent FSGS following kidney transplantation and should be started as soon as possible. The number of plasmapheresis sessions used to achieve remission should be adjusted according to response rather than adhering to a fixed protocol. Received: 22 November 1999 / Revised: 2 March 2000 / Accepted: 6 March 2000     

Plasmapheresis therapy for rapidly progressive Henoch-Schönlein nephritis

Six Japanese children with rapidly progressive Henoch-Schönlein purpura nephritis (HSPN) received multiple drug therapy combined with plasmapheresis (PP). After five courses of PP, multiple drug therapy, including methylprednisolone and urokinase pulse therapy, oral prednisolone, cyclophophamide, dipyridamole, and warfarin was given. At presentation, urine protein excretion and histological indices of the mean activity and chronicity were 245±101 mg/m² per hour, 6.6±1.2, and 1.5±1.3, respectively. After 6 months of therapy, urinary protein excretion had decreased significantly (P<0.001). The activity index decreased significantly at the second renal biopsy performed at a mean interval of 4.3 months after the first (2.8±1.4, P<0.05), while the chronicity index did not change. At the most recent observation, all showed clinical improvement. Two patients had normal urine, three had proteinuria of <20 mg/m² per hour, one had proteinuria of >20 mg/m² per hour, and none had renal insufficiency. Although this case series is without controls, our treatment protocol may be of benefit to children with rapidly progressive HSPN.     

Long-term plasmapheresis and protein A column treatment of recurrent FSGS

Transient or intermittent plasmapheresis with concurrent immunosuppressive therapy is thought to be beneficial in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the early post-transplant period. The results of long-term (6-year) plasmapheresis therapy, in a 9-year-old female with an immediate recurrence of FSGS [urinary protein/urinary creatinine (UP/UC)=17.7] after cadaveric renal transplant, are presented. A 4-week plasmapheresis course induced a decline in the proteinuria, but a relapse occurred after cessation of plasmapheresis. Addition of protein A column therapy led to a further decrease in the proteinuria, to a non-nephrotic range. Long-term control of the nephrotic syndrome was established using a chronic treatment regimen consisting of a single-volume plasmapheresis, followed by a protein A column treatment, performed on sequential days every 3–4 weeks. Mean UP/UC values decreased to 1.15±0.9. A course of cyclophosphamide was successfully used to control a worsening of proteinuria 4 years post transplant. Although sequential renal biopsies demonstrated progressive glomerular sclerosis, the patient’s mean calculated creatinine clearance only modestly declined from 78.3 ml/min per 1.73 m², at the time of transplantation, to 62.7 ml/min per 1.73 m², 6 years later. This patient demonstrated dependence on plasmapheresis/protein A column therapy to maintain a clinical remission of her FSGS recurrence. While long-term plasmapheresis and protein A column therapy in combination with immunosuppressive therapy reversed the effects of uncontrolled nephrosis and possibly facilitated long-term renal allograft survival, the glomerular sclerosis continued to progress. Received: 4 April 2001 / Revised: 15 June 2001 / Accepted: 15 June 2001     

Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade

Steroid-resistant nephrotic syndrome of childhood poses a dilemma in attempting to balance toxicity of medications against long-term prognosis. This report presents our preliminary experience with the novel use of combined mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the treatment of nine children and young adults with focal glomerulosclerosis (FSGS). All patients were steroid resistant and had failed conventional treatment regimens. Prior to the initiation of the MMF-AB protocol, the patients were pre-treated with weekly intravenous methylprednisolone (MP) (15 mg/kg per week) for 4–8 weeks. Angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blockers were begun when intravascular volume was restored. MMF was given at a dose of 250–500 mg/m² per day. Proteinuria, as measured by urine protein/creatinine ratios (Up/c), decreased by 43% following MP (P<0.05). After 6 months of MMF-AB protocol, the Up/c was 72% below baseline (P<0.01). This level was maintained for a minimum of 24 months of observation. Similarly, hyperlipidemia, as measured by total cholesterol and triglycerides, improved significantly with treatment (536±163 to 265±70 mg/dl, 447±168 to 230±92 mg/dl, respectively, P<0.01). Our data support the use of MMF and AB for treatment of steroid-resistant FSGS when other conventional treatments have failed and/or induced toxicity.     

One-center experience with cyclosporine in refractory nephrotic syndrome in children

 Uncontrolled or refractory nephrotic syndrome (NS), seen in a variety of glomerular disorders, leads to end-stage renal disease (ESRD). This study describes the use and efficacy of cyclosporine (CSA) for the treatment of refractory NS in 83 children seen over a 10-year period. The histological diagnosis leading to the NS was focal segmental glomerulosclerosis (FSGS) in 51% (n=42), IgM nephropathy in 20% (n=17), membranoproliferative glomerulonephritis in 10% (n=8), lupus nephritis in 6% (n=5), human immunodeficiency virus (HIV) nephropathy in 5% (n=4), minimal change disease in 7% (n=6), and membranous nephropathy in 1% (n=1) of patients. During CSA therapy the mean proteinuria of the study population decreased from 5.14 g/24 h (4.80 g/m² per 24 h) to 1.23 g/24 h (0.92 g/m² per 24 h) (P<0.001), the mean serum albumin increased from 2.13 g/dl to 3.53 g/dl (P<0.001), the mean serum cholesterol decreased from 364 mg/dl to 223 mg/dl (P<0.001), and the mean serum creatinine increased from 0.77 mg/dl to 1.2 mg/dl (P<0.01). When analyzed by histological diagnosis, similar significant trends of reduction in proteinuria were seen in all but the lupus group. There was a rise in serum creatinine following the use of CSA in patients with FSGS, lupus nephritis, and HIV nephropathy; however the elevated serum creatinine was only significant in patients with FSGS. At the end of the study period, 20 patients had reached ESRD, of which 11 had FSGS, 5 had lupus nephritis, and 4 were patients with HIV nephropathy. Fifty-four patients were in remission at the end of the study period (48 with proteinuria <100 mg/24 h and 6 with proteinuria <500 mg/24 h). In conclusion, among children with refractory NS, CSA induced a remission in a large proportion. However toxicity, as noted by the rise in serum creatinine, was observed in several patients. Since this toxicity may be drug induced or a natural progression of the disease, careful monitoring and close follow-up are essential. Received: 21 October 1997 / Revised: 30 April 1998 / Accepted: 29 May 1998     

Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab

A 22-year-old patient whose primary kidney disease was focal segmental glomerulosclerosis (FSGS) developed severe recurrence of proteinuria (up to 57 g/24 h) immediately after a haploidentic living donor kidney transplantation despite pre-operative plasmapheresis. The immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil, basiliximab and steroids. He underwent 10 plasmapheresis sessions in the first 3-week post-transplantation. In addition, he received 2 i.v. doses of rituximab (RTX) 600 mg (375 mg/m(2)) on days 7 and 15. Proteinuria decreased below nephrotic range at day 14 and serum creatinine returned progressively to normal values. A short course of oral ciclophosphamide (100 mg/j) was administrated between days 22 and 40 and three additional plasmapheresis sessions on days 34, 39 and 49. This strategy allowed obtaining sustained full remission of the nephrotic syndrome (NS) and excellent graft function, which persists over 2 years after transplantation. No notable adverse events related to RTX or plasmapheresis were observed. This case suggests that RTX associated with plasmapheresis may be an effective treatment of recurrent NS because of FSGS.     

Growth hormone therapy and lipid profile in children on chronic peritoneal dialysis

The aim of the study was to assess the effect of recombinant human growth hormone (rhGH) on serum lipids in children treated with chronic peritoneal dialysis. We studied 26 patients aged 5-18 years, including 13 patients treated with rhGH at a dose of 1-1.1 IU/kg per week for 6 months and a control group of 13 patients. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), HDL-C, triglycerides (TG), apolipoproteins A-I and B-100 (apoA and apoB), lipoprotein (a) [Lp(a)], total protein, albumin, urea, and creatinine levels were measured in all children at baseline and at 1, 3, and 6 months of follow-up. We found a significant increase in the TG level after 1 month of administration of rhGH in the treatment group compared with both baseline (218.8+/-49.2 mg/dl vs. 175.9+/-71.9 mg/dl, respectively, P<0.05) and the control group at 1 month of follow-up (146.5+/-44.3 mg/dl, P<0.001). We found no change in TC, LDL-C, HDL-C, apoA, and Lp(a) levels during treatment with rhGH. These data suggest that administration of rhGH to children treated with peritoneal dialysis results in only a transient increase of serum TG level and has no effect on TC, LDL-C, HDL-C, apoA, and Lp(a) levels.     

Quantification of proteinuria in children using the urinary protein-osmolality ratio

A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m²/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061±0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073±0.014. Twenty-four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78±1.10 and Uprot/Uosm was 4.42±1.34. Twenty- four hour urinary protein excretion in group 2 was 1483.6±303.7 mg/m²/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r= 0.87, P<0.001 and r=0.88, P<0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m²/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children. Received: 13 April 1999 / Revised: 23 February 2000 / Accepted: 15 August 2000     

Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis

Relapse of focal segmental glomerulosclerosis (FSGS) after renal transplantation is 20-40%. Recurrence after a first relapse is 80%. The only current treatment is plasmapheresis and/or cyclophosphamide. We report successful treatment of a second relapse in a 48-year-old patient. At age 33, FSGS was diagnosed. The patient began hemodialysis 1 year later. In her first renal transplant, she developed recurrent FSGS and reached terminal transplant failure 3 years later. Eight years later, a second transplant was performed. Immunosuppressive regimen: steroids, mycophenolate mofetil (MMF), tacrolimus (TAC), and rabbit anti-thymocyte globulin. Proteinuria of 2-6 g/day was detected and a biopsy showed recurrent FSGS. Plasmapheresis was started without success. Another biopsy still showed FSGS. The patient received two doses of rituximab (375 mg/m2 each) i.v. Three weeks later, proteinuria was 350 mg/day (serum-creatinine 1.6 mg/dl). Twelve months later, proteinuria was at 90 mg/day. Rituximab might be an option for recurrent FSGS after renal transplantation.     

Effects of fluvastatin on plasma lipid abnormalities in hemodialysis patients with chronic renal failure

Fluvastatin, an HMG-CoA reductase inhibitor, was administered at a dosage of 20 mg/day for 24 weeks to 11 hemodialysis patients with a high plasma total cholesterol (TC) level (> or = 220 mg/dl). Serum lipids, apolipoprotein, and malondialdehyde (MDA) levels were measured every 12 weeks. After 24 weeks of fluvastatin administration, the TC level had decreased by 10.5% (238 +/- 15 mg/dl-->203 +/- 25 mg/dl), the low density lipoprotein cholesterol (LDL-C) level had decreased by 16.2% (142 +/- 32 mg/dl-->119 +/- 26 mg/dl), and the HDL-C level had increased by 23.4% (47 +/- 15 mg/dl-->58 +/- 19 mg/dl). These changes were statistically significant and resulted in a reduction of the atherogenic index (AI: TC-HDL-C/HDL-C). The triglyceride (TG) level did not change significantly. The apolipoprotein A1 level increased by 9.1% (121 +/- 22 mg/dl-->132 +/- 20 mg/dl) and the apolipoprotein B level decreased by 20.2% (114 +/- 25 mg/dl-->91 +/- 20 mg/dl). The MDA level also decreased significantly (1.16 +/- 0.92 nmol/ml-->0.58 +/- 0.38 nmol/ml). No particular side effects were observed during the 24 weeks of fluvastatin administration. In conclusion, fluvastatin may play an important role in preventing significant oxidative stress and was shown to be safe and effective in reducing the TC, LDL-C, MDA and AI levels in dialysis patients with hypercholesterolemia. The possibility that this improvement in the plasma lipid profile of dialysis patients may decrease atherogenic complications requires further investigation, including long-term clinical observations.     

Risk factors for hyperlipidemia in long-term pediatric renal transplant recipients

Hyperlipidemia (HL) is a common problem in adult renal transplant (TP) recipients, contributing to an increased risk of cardiovascular disease and chronic TP nephropathy. There are multiple causes of HL post renal TP in adult patients, including pre TP HL, immunosuppressive agents, renal dysfunction, hypoalbuminemia secondary to nephrotic syndrome, obesity, and conditions that lead to end-stage renal disease (ESRD). We evaluated the incidence and risk factors of HL in 62 pediatric renal TP recipients (15.4±4.2 years, range-3.0–22.3 years) with long-term (6.7±3.1 years) functioning [glomerular filtration rate (GFR) 66.7±23.2 ml/min per 1.73 m²] allografts. The mean serum cholesterol (C) level was 205.5±43.6 mg/dl. Thirty-two patients (51.6%) exhibited elevated serum C levels. The mean serum triglyceride (TG) level was 157.3±88.4 mg/dl. Serum TG levels were elevated in 32 patients (51.6%). In patients with elevated serum levels of either C or TG, the mean low-density lipoprotein level (LDL) was 138.6±44.1 mg/dl (normal <130 mg/dl) and the high-density lipoprotein (HDL) level 54.6±15.9 mg/dl (normal>34 mg/dl). Of those patients studied, 45.5% had high LDL levels, whereas 9.1% exhibited low HDL levels. The two risk factors for elevated serum C levels in our patient population were pre-TP HL and increased years since TP. The only risk factor for elevated serum TG levels was reduced GFR. A family history of HL had a significant deleterious impact upon serum levels of C (P=0.01), but did not affect serum TG levels (P=0.7). Years on dialysis prior to TP, history of prior TP, gender, body mass index, and disease leading to ESRD had no influence upon the development of post-TP HL. We conclude that post-renal TP HL is a significant problem in pediatric renal TP recipients. Received: 13 January 1999 / Revised: 19 May 1999 / Accepted: 21 May 1999     

Cardiovascular risk factors and diseases after renal transplantation

Cardiovascular disease is a leading cause of death after renal tranpslantation (tpx), and the incidence is considerably higher than in the general population. Objective To evaluate the incidence of atherosclerotic cardiovascular complications after tpx, the prevalence of cardiovascular risk factors, prior to and following tpx, and the association between the risk factors and complications. Patients and methods Analysis of atherosclerotic cardiovascular diseases (coronary artery disease, cerebral and peripheral vascular disease) and cardiovascular risk factors before and after transplantation in 427 renal transplant recipients between 1987 and 1992 (mean age at transplantation 45±12 years, 58% male, 7% diabetics) with a mean post-transplant follow-up of 29±20 months. Results Following tpx 11.7% developed atherosclerotic cardiovascular diseases, the majority coronary artery disease (9.8%). The comparison of risk factors 12 months before and 24 months following transplantation showed: prevalence of systemic hypertension (from 73% to 85%), diabetes mellitus (from 7% to 16%) and obesity with a body mass index >25 kg/m² (from 26% to 48%) had increased significantly whereas the number of smokers halved to 20%. Triglycerides decreased significantly (from235 mg/dl to 217 mg/dl). Totaland HDL cholesterol rose significantly (from 232 mg/dl to 273 mg/dl and from 47 mg/dl to 56 mg/dl, respectively). LDL cholesterol increase was significant (from 180 mg/dl to 189 mg/dl). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus (DM), smoking, total cholesterol ≥200 mg/dl, LDL cholesterol>180 mg/dl, HDL cholesterol ≤55 mg/dl, fibrinogen ≥350 mg/dl, body mass index>25 kg/m², serum uric acid >6.5 mg/dl and with more than two antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3, age>50 years (RR=2.7), body mass index>25kg/m² (RR=2.6), smoking (RR=2.5), LDL cholesterol>180 mg/dl (RR=2.3) and uric acid>6.5 mg/dl as independent risk factors. Conclusions The high incidence of cardiovascular disease following renal transplantation is mianly due to a high prevalence and accumulation of classical risk factors before and following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high risk population.     

Lipoprotein lipid abnormalities in healthy renal transplant recipients: persistence of low HDL2 cholesterol

There is disagreement about the prevalence and character of lipoprotein lipid abnormalities in renal transplant patients. To test the hypothesis that these abnormalities may be related to the coexistence of medical conditions and medications which affect lipoprotein metabolism in these patients, triglyceride (TG), cholesterol (C), high-density lipoprotein (HDL) and HDL-C subfractions were measured in 26 transplanted patients (10 F/16 M), control subjects matched for age, sex, weight and race and uremic patients being treated with hemodialysis. Female transplant recipients had higher TG (181 +/- 47 vs. 68 +/- 6 mg/dl; p less than 0.001), C (242 +/- 19 vs. 165 +/- 9 mg/dl; p less than 0.01), and low-density lipoprotein (LDL)-C (155 +/- 15 vs. 93 +/- 8 mg/dl; p less than 0.01) than controls. Levels of HDL-C were similar, but HDL2 was significantly lower in the transplanted patients (9 +/- 2 vs. 19 +/- 2 mg/dl; p less than 0.01). Compared to the uremic patients, female transplanted patients had higher C (242 +/- 19 vs. 178 +/- 22 mg/dl; p less than 0.01), LDL-C (155 +/- 15 vs. 94 +/- 18 mg/dl; p less than 0.01), HDL-C (51 +/- 5 vs. 32 +/- 4 mg/dl; p less than 0.001) and HDL3-C (42 +/- 4 vs. 26 +/- 2 mg/dl; p less than 0.001); however, HDL2-C levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children

Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r²=0.842, P<0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m²/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children’s body height and gender.     

Long-term efficiency, biocompatibility, and clinical safety of combined simultaneous LDL-apheresis and haemodialysis in patients with hypercholesterolaemia and end-stage renal failure

Three hypercholesterolaemic patients on maintenance haemodialysiswith angiographically proven coronary artery disease were treatedin a once-a-week schedule by combined, synchronous lipid apheresis(using heparin-induced extracorporeal LDL precipitation) andhaemodialysis (HELP/HD) for 65–104 weeks. Clinical side-effectswere few and mostly related to high ultrafiltration rates inpatients with low compliance regarding interdialytic fluid restriction.Biocompatibility of the procedure was shown to be good and bloodcell losses, leukocyte (elastase release) and thrombocyte (ß-thromboglobulinextrusion) as well as complement (C3a formation) activationwere minimal. Interestingly, most of the C3a generated in theextracorporeal HELP circuit was immediately removed again inthe precipitate filter. In the pseudo-steady-state after 3 monthsof regular therapy, acute haematocrit-corrected reduction ofplasma components after the session compared to pre values wereabout 55% for the risk factors LDL cholesterol (LDL-C), lipoprotein(a)(Lp(a)), and fibrinogen (FIB) with good recovery of HDL-C andother proteins. Urea, creatinine, and phosphate eliminationwas similar to normal haemodialysis. Mean interapheresis values of risk factors after one (n=2) andtwo (n=1) years of treatment were crucially dependent upon ultrafiltration(UF); thus, in two patients with high UF LDL-C concentrationsamounting to 185 and 220mg/dl at baseline and were reduced toabout 135mg/dl LDL-C, while in the patient with low UF the reductionwas from 231 mg/dl to 80 mg/dl. The atherogenic index (LDL-C/HDL-C)was reduced from 6.4 and 5.1 to about 4.3 in patients with highUF, from 6.1 to 3.3 in the patient with low UF. Fibrinogen andLp(a) were normalized in all patients. In summary, the combined HELP/HD treatment in hypercholesterolaemicdialysis patients proved to be a safe, effective, and selectiveprocedure for lipoprotein and fibrinogen normalization withexcellent biocompatibility and good clinical patient tolerance,providing a tool ready for future atherosclerosis regressionstudies in ESRD patients.     

Pulse cyclophosphamide for steroid-resistant focal segmental glomerulosclerosis

 We report the response of ten patients (6 male, 4 female) with steroid-resistant focal segmental glomerulosclerosis (FSGS) to treatment with intravenous pulse cyclophosphamide (IVCP) together with oral prednisone. All patients had been treated with 60 mg/m² oral prednisone daily for 2 months upon initial presentation. IVCP was given monthly at a dose of 500 mg/m² over 6 months. Oral prednisone was given concurrently at 60 mg/m² daily for 2 months and then on alternate days for 4 months, followed by 30 mg/m² on alternate days for 6 months. Prednisone was then tapered monthly by 10 mg and finally discontinued. Five patients failed to respond to steroids from the onset and were considered as primary steroid resistant. Two of these patients achieved sustained remission after IVCP, one patient showed a partial response, with loss of edema, normalization of serum albumin, and persistent proteinuria, while two patients showed no response to IVCP. The other five patients had achieved remission after 2 months of daily prednisone at 60 mg/m² upon initial presentation, but had suffered from more than three relapses per year and had eventually become steroid resistant. They were considered secondary steroid resistant. All five patients achieved sustained remission after IVCP. None of our patients suffered from adverse effects of IVCP. We suggest IVCP as an adjunctive therapy for steroid-resistant FSGS, particularly for patients with secondary steroid resistance. Received: 20 November 1997 / Revised: 30 June 1998 / Accepted: 1 July 1998     

Can Kunxian Capsule,a Novel Tripterygium Preparation be Used as an Adjuvant Treatment of Early Recurrent Focal Segmental Glomerular Sclerosis After Renal Transplantation? A Case Report

Focal segmental glomerular sclerosis (FSGS) tends to recur after kidney transplantation, particularly when genetic testing is negative. Once the recurrence happens, the renal graft function can rapidly become impaired, following a massive urine protein loss. Despite intensive plasmapheresis and high-dose rituximab treatment, the complete remission rate remains below 50%. The Kunxian capsule, representing a new generation of tripterygium preparation, has shown promising results in controlling proteinuria in patients with IgA nephropathy. It is unclear whether Kunxian capsule treatment would also produce a favorable response in cases of FSGS recurrence. Here we report favorable results with this approach in a patient with early recurrent FSGS after kidney transplantation; we treated this patient successfully with a Kunxian capsule, a low dose of rituximab (200 mg), and reduced sessions of plasmapheresis. Complete remission, with a 90% reduction in total urine protein (0.81 g/24 h vs 8.3 g/24 h), was achieved within 2 weeks post-treatment. Of interest, the complete remission state in this patient has been maintained over 20 months with continuous administration of Kunxian capsules after the cessation of plasmapheresis. The potential mechanisms involved here include direct podocyte protection and the anti-inflammatory and immunosuppressive properties of triptolide in the Kunxian capsule. Our case may offer a new reference option for treating recurrent FSGS in the future.     

Safety and efficacy of rosuvastatin therapy for the prevention of hyperlipidemia in adult cardiac transplant recipients.

BACKGROUND: Hyperlipidemia after orthotopic heart transplantation (OHT) is associated with immunosuppression. Many OHT patients have increased lipid levels above published guidelines despite treatment with high doses of statins. Treatment with rosuvastatin (ROS) in OHT patients has not yet been evaluated. Therefore, we assessed its efficacy and safety in an OHT population. METHODS: Twenty-one OHT recipients, median age 66 years, whose lipid levels were sub-optimal on the highest tolerated doses of statins, received ROS in addition to standard immunosuppression. Total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), liver transaminases (AST) and creatinine kinase (CK) were measured before and during treatment with ROS. RESULTS: After 6 weeks on an average ROS dose of 10 mg/day, a TC:HDL-C ratio of <4 was reached in 76% of patients, and 70% of patients reached an LDL-C level of <2.5 mmol/liter (100 mg/dl). TC decreased to <5.2 mmol/liter (200 mg/dl) in 80% of patients and TG decreased to <2 mmol/liter (175 mg/dl) in 61% of patients. Except for the HDL-C increase, all changes were statistically significant. The decrease in the median TC:HDL-C ratio between baseline and 6 weeks was also statistically significant (p = 0.001). There were no significant changes in CK or AST levels, and no clinical evidence of myositis. One patient developed myalgia and 2 were withdrawn from the study because of mild elevation of CK (<3-fold upper limit of normal [ULN]). CONCLUSIONS: In the setting of tertiary referral centers, ROS appears to be safe and effective in lowering LDL-C in OHT recipients in whom treatment with other statins failed to achieve target LDL-C. No evidence of liver or muscle dysfunction was noted. Long-term studies are needed to ascertain the effect of ROS therapy on incidence of coronary artery disease (CAD) in this population.     

Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass

POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low-density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk.     

Renal effects of continuous infusion of recombinant interleukin-2 in children

Recombinant interleukin-2 (rIL-2) is a new promising treatment for cancer, but is associated with severe renal toxicity. This study is the first to analyse the renal effects of rIL-2 in children. Twenty-one cycles of continuous rIL-2 infusion were studied in 15 patients; mean age was 6.9 years and average weight 18.9 kg. Interstitial fluid retention and oliguria (baseline, 1.7 ml/kg per hour; nadir, 0.5 mg/kg per hour) were associated with hypotension (baseline, 101/56 mm Hg; nadir, 85/43 mm Hg) and decreased intravascular volume (plasma renin activity increased×10). Weight gain (+7.9%) was observed in 13 cycles whereas weight loss (–6.3%) was shown in 8 cycles because of digestive and cutaneous losses, mainly in the youngest patients. This prerenal azotaemia was characterized by a decrease in creatinine clearance (from 101 to 36 ml/min per 1.73 m²) and a low fractional excretion and sodium (FE_Na) (from 0.70% to 0.09%).Hypotension and hypovolaemia needed vascular filling (n=12), dopamine (n=7) and interruption of rIL-2 (n=2). Most abnormalities occurred as early as day 2 of therapy and were always reversible after a short period with sodium leakage (diuresis=2.2 ml/kg per hour, FE_Na=2.01%). Hypophosphataemia was associated with low urinary excretion of phosphorus, suggesting an increased uptake of inorganic phosphorus by rapidly proliferating lymphoid cells.