2nd posting:Meds & Treatment of Nephrotic Syndrome

Dyad 4
Balajadia, Bond
Zano, Alexis

Comparison between a 4-week versus 6-week Induction Therapy of Prednisone a 60 mg/m2/day on Newly Diagnosed Nephrotic Syndrome

Nephrotic Syndrome is applicable to any condition with proteinuria, hypoalbuminemia, edema and hypercholesterolemia with reported incidence of 2-7/100,000 population in children. This study aimed to determine the more-effective induction therapy between a 4-week treatment of 60 mg/m2/day Prednisone and a 6-week treatment of same dose that would render remission with minimum side effects. This study specifically aims to compare the period of remission and the frequency of relapses among patients treated with a 4-week versus 6-week induction treatment of Prednisone and to record side effects of 4-week versus 6-week therapy of Prednisone. The design utilized for this study was Prospective Randomized Controlled study, with samples divided into two groups. The first group was given 60mg/m2/day of Prednisone for 4 weeks and the second group was given 60mg/m2/day for 6-weeks.

The results were thirty-five patients received the 4-week induction therapy while 30 patients received the 6-week induction therapy. The period of remission, number of relapses and side effects were monitored. There was no significant difference between the mean periods of remission. However, there was 50% decrease in relapse rates in 6-week induction therapy. There was no significant increase in the incidence of side effects in 6-week induction therapy. Side effects encountered were hypertension, behavioral changes, moon fascie, pimples and striae.

We therefore conclude that based on the data presented, it confirm that the longer course of steroids for the initial treatment of steroid-sensitive nephritic syndrome results in a higher proportion of sustained remission with no side effects. We highly recommend that this kind of intervention should be rendered to newly diagnosed case of Nephrotic Syndrome in children for better control of proteinuria. The significance of this study in the field of Nursing Profession is that it will serve as preliminary point to make further studies in the management and care of Nephrotic syndrome patients, specifically the development of much improved nursing care plan for this kind of patients.

Reference: Tadoy et. al. Comparison between a 4 week versus 6 week Induction Therapy of Prednisone a 60 mg/m2/day on Newly Diagnosed Nephrotic Syndrome. NKTI Proceedings 5. August 2003

Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
1: Pediatr Nephrol. 2007 Dec;22(12):2059-65. Epub 2007 Oct 16

The management of patients with steroid-dependent nephrotic syndrome (SDNS) refractory to treatment with long-term steroids, levamisole and cyclophosphamide is difficult. We report our experience on long-term treatment with mycophenolate mofetil (MMF) and alternate-day prednisolone in 42 patients with SDNS previously treated with levamisole (n = 35) and/or cyclophosphamide (n = 37). The mean age (range) at onset of nephrotic syndrome was 37 (13-92) months and at treatment with MMF 104.7 (32-187) months. MMF was administered at a mean daily dose of 26.5 (16.6-31.3) mg/kg for 14.3 (6-45) months. The mean 6-monthly relapse rates decreased from 3.0 episodes before therapy to 0.9 episodes in the first 6 months, 0.7 in next 6 months, and 0.3 in those treated longer than 12 months (P < 0.0001). While on therapy, 32 (76.2%) patients showed 50% or more reduction in relapse rates, and nine (21.4%) had sustained remission. The cumulative dose of prednisolone declined significantly from 0.6 mg/kg per day before to 0.3 mg/kg per day while receiving MMF. Prednisolone requirement was reduced by 50% or more in 16 patients and between 40% and 50% in eight patients. Treatment continuation beyond 12 months resulted in sustained steroid sparing and reduced need for alternative treatments while maintaining low relapse rates. No patients had diarrhea, hematological abnormalities, or impaired renal function. This data confirms the efficacy and safety of treatment with MMF and tapering doses of alternate-day prednisolone in patients with SDNS and supports its use for longer than 12 months.

Dyad 6 guomanman and chenya



Type I membranoproliferative GN often progresses slowly; type II progresses more rapidly. In general, the long-term prognosis is poor. End-stage renal disease occurs in 50% of patients at 3 to 5 yr and in 75% at 10 yr; at 5 yr, only 25% have normal renal function. Spontaneous remission occurs in < 5%. Type I membranoproliferative GN recurs in 30% of kidney transplantation patients; type II recurs in 90%.

Specific therapy is probably not indicated in patients with non-nephrotic–range proteinuria because the disease usually progresses slowly. In nephrotic children, treatment with prednisone Some Trade Names DELTASONE Click for Drug Monograph 2.5 mg/kg po once/day on alternate days (maximum 80 mg) for 1 yr, followed by tapering to a maintenance dose of 20 mg on alternate days for 3 to 10 yr, may stabilize renal function. However, corticosteroid treatment may retard growth and cause hypertension. In adults, dipyridamole Some Trade Names
PERSANTINE Click for Drug Monograph (225 mg po once/day) with aspirin Some Trade Names BUFFERIN ECOTRIN GENACOTEClick for Drug Monograph (975 mg po once/day) for 1 yr seems to stabilize renal function at 3 to 5 yr, but at 10 yr there is no difference from placebo. Prolonged therapy may be required. Alternate therapies include α-interferon (with addition of ribavirin Some Trade NamesVIRAZOLE Click for Drug Monograph if creatinine clearance is > 50 mL/min) for hepatitis C virus–associated disease and plasmapheresis with corticosteroids for concomitant severe cryoglobulinemia or rapidly progressive GN. ACE inhibitors may decrease proteinuria and help control hypertension.

Response
D2- Gil Legarda and Joanalyn Balino

Title: Initial Treatment of Idiopathic Nephrotic Syndrome in
Children: Prednisone versus Prednisone Plus Cyclosporine A:
A Prospective, Randomized Trial

Peter F. Hoyer and Johannes Brodehl


Hoyer and Brodehl made a prospective, randomized trial to test the hypothesis that the amount of initial immunosuppression has an impact on subsequent relapses, They wanted to test whether Prednisone plus Cyclosporine A(CsA) have an efficacy in reducing the number of relapses, mean relapse rates per patient. They also wanted to assess the safety and the tolerability of the total immunosuppressive load. And they would like to know the specific CsA-associated side effects. A total of 104 patients participated in this Randomized trial; 55 were randomly assigned to the Pred group and received the standard treatment of 60 mg/m2 per day of prednisone for 6 wk followed by 40 mg/m2 per 48 h for 6 wk. The Pred+ CsA group that consist of 49 patients received the same prednisone regimen plus CsA with a dose of 150 mg/m2 per d for 8 wk. The numbers of patients who remained for follow-up in the Pred group and the Pred_CsA group after 6 months were 53 versus 49, after 12 months were 46 versus 45, after 18 months were 45 versus 44, and after 24 months were 43 versus 44. The Inclusion criteria include: (1) pediatric patients with age ranging from 1 to 16 yr of age with first manifestation of NS with proteinuria 40 mg/m2 per h; (2) with a serum albumin concentration of 25 g/L; (3) a preserved GFR with a creatinine clearance of 68 ml/min per 1.73 m2 ; (4) No history of corticosteroids or immunosuppressive agents treatment; (5) they should not have contraindication to corticosteroid therapy.The exclusion criteria include: (1) with a low c3-complement; (2) With postinfectious glomerulonephritis;(3) those who had systemic diseases such as lupus erythematodes, diabetes, amyloidosis, vasculitis, Scho¨nlein-Henoch nephritis, metabolic or toxic nephritis, hepatitis B, or hereditary glomerular diseases; (4) Patients who did not respond within 4 wk were defined as not steroid sensitive were excluded from the study.


The median cumulative sustained remission time in the Pred group after completion of the initial treatment, was 12.5 months with 95% confidence interval [CI] 5.9 to 19.1 months and in the PredCsA group was 22.8 months with 95% CI 11.6 to 34.0; (P =0.1). The differences after 6 and 12 months after initial treatment between both treatment groups were significantly different (P = 0.05). Following 18 and 24 months, the differences was gone. Cyclosporine A treatment was well tolerated. There were no reported Infections that were related to the combined prednisone plus CsA. One of the major concerns of CsA treatment was nephrotoxic side effects, but there were no evidence of deterioration on kidney function. The serum creatinine was equal in both groups (46.2± 10.0 mol/L in the Pred group and 48.2 ±11.1 mol/L in the Pred_CsA group). Statistical analysis to risk factors for relapses revealed that only age and protein concentration at initial manifestation were significant risk factors. A higher risk for relapses revealed in children who were younger than 7 yr and had an initial protein concentration of 44 g/L. In 2-yr observation time, there was a significantly better sustained remission rate with initial CsA treatment P = 0.03. Age 2 to 3-yr-old have 4 times higher risk for experiencing a relapse than for those who are older than 7-yr-old.



A lower cumulative dose of steroids needed to treat relapses counterbalanced the relatively high rate of steroid side effects. Add-on immunosuppressive drug in avoiding higher doses of steroids has been shown to be effective in preventing relapses. Cyclophosphamide treatment might not be an option to patients at initial presentation for the reason that approximately 50% will receive an unnecessary potentially harmful therapy. There was an effect on the number in subsequent relapses that lasted for 1 yr with 8 weeks of add-on treatment with CsA at initial manifestation of steroid sensitive Nephrotic syndrome. The protocol (Predisolone+ Cyclosporine A) might not be recommended generally for patients because of the attenuation of the effect after 2 years, its side effects, and the need to control blood levels. Further studies will be needed that ought to stratify pediatric patients with NS according to age groups and intensified treatment should focus on the younger group.

Hoyer, P., and Brodehl, J. (2005). Initial Treatment of Idiopathic Nephrotic Syndrome in Children: Prednisone versus Prednisone Plus Cyclosporine A:
A Prospective, Randomized Trial. J Am Soc Nephrol 17: 1151-1157, 2006. Retrieved June 24, 2009 from http://jasn.asnjournals.org/cgi/reprint/17/4/1151?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&minscore=5000&resourcetype=HWCIT

Mycophenolate mofetil in the treatment of nephrotic syndrome
S Saxena*, S Virmani**, K Singh***, KK Malhotra****

The usual problem nowadays relating to treatment of nephrotic syndrome is resistance to conventional treatments with drugs like steroids and cyclophophamide. Nephrologists discovered new agents such as cyclosporine but showed not an ideal treatment due to the side effects. The study was conducted in order to evaluate the efficacy of Mycophenolate mofetil (MMF) in the treatment of nephrotic syndrome. The participants were selected must be diagnosed with nephrotic syndrome through biopsy and is empirically resistant to conventional treatment regimen. 10 participants were identified and consented to join the study. The patients underwent treatment with MMF for a year then they were interviewed to discuss the unproven efficacy as well as the long-term side-effects of MMF therapy. the initial dose of MMF given to the participants was 30mg/kg/day and was subsequently increased to 40mg/kg/day not unless tolerated. Treatment will be discontinued temporarily once the client would have decreased leukocyte count, patient developed fever, or experienced unacceptable GI symptoms. Treatment will be stopped if the client’s liver enzyme will be elevated twice the normal levels.

It is found out in the study that there were significant enhancement in the amount of protein present in the urine along with the improvement of serum albumin levels and creatinine clearance among the participants. The incidence of toxicity based on reports was low. MMF therapy also shows to be effective as a monotherapy among patients with nephrotic syndrome due to its major steroid sparing effect.

There are certain limitations seen in this study. One is that the research only comprises of a small number of participants and this study is not a controlled clinical trial. This study does not confirm the efficacy of MMF in other diseases such as glomerular diseases. Long term side effects of the medications were not also mentioned in the study. Based on the result finding, it is recommended that there should be a follow up research inline with this study in order to have a stronger empirical basis for this type of treatment. Hence, the physiologic effects of this medication is beneficial to nephrotic syndrome clients, still further clinical trials should be performed.

References:
Authors and disclosures
*Senior consultant, **Senior Resident, ***Consultant, ****Senior consultant,
Pushpawati Singhania Research Institute for Liver, Renal & Digestive Disease, New Delhi

Nonspecific treatment of nephrotic syndrome is aimed at complications like hypertension. Specific treatment addresses underlying causes, which are determined by kidney biopsy.

Nonspecific Treatment
Controlling hypertension is essential in reducing proteinuria. This is accomplished with angiotensin converting enzyme (ACE-1) inhibitors. ACE-1 inhibitors are the preferred blood pressure lowering medication because they provided added protection to the kidneys. These drugs interfere with the production of angiotensin II (AII), a chemical (vasoactive) produced in the body. AII causes vascular constriction, which increases blood pressure, including pressure in the glomeruli. This causes scarring of the kidney and exacerbates proteinuria, which accelerates the loss of renal function. ACE-1 inhibitors encourage circulation, lower blood pressure in the body, and decrease pressure in the glomeruli. This decreases protein spillage and helps to delay progressive scarring of the glomeruli.
Patients with hypertension benefit from ACE-1 inhibitors, as aggressive blood pressure control is key to protecting the kidneys and the cardiovascular system. The goal is to lower the systolic blood pressure below 130 and the diastolic below 80.
ACE-1 inhibitors cause a dry cough in approximately 8% of patients who take them.
ACE-1 inhibitors are given in the highest dose tolerable to ensure kidney protection. If a patient develops a cough, a new class of drugs may be used, known as angiotensin receptor blockers (ARB). ARBs work by blocking angiotensin receptors, which blocks the effects of angiotensin after it is produced. They offer the same kidney protection as ACE-1 inhibitors without causing cough. If tolerable, ARBs may be combined with an ACE-1 inhibitor for added benefit.
Treating high cholesterol (hypercholesterolemia) typically involves medication and proper diet.
It is generally considered healthy to eat one gram of protein daily for every kilogram of body weight; physicians usually help their patients define a diet that is appropriate for kidney health.

Specific treatment is given for the following underlying causes of nephrotic syndrome:
Diabetes
Glomerular disease
Minimal change disease
Renal failure
Treating minimal change disease in children usually involves the use of diuretics to reduce edema and a corticosteroid called prednisone (Liquid Pred), which usually resolves proteinuria in a couple of weeks. Corticosteroids heal the ongoing damage at the level of the glomerular basement membrane (i.e., they patch the holes that are allowing the proteins to leak through).
About 30% of children treated with prednisone have no recurrence of disease, roughly 20% relapse after several months, and the remaining 50% relapse a short time after discontinuing the medication.

Gluococorticoid therapy has become the primary agent of choice in the treatment of patients with nephrotic syndrome. In most cases, oral prednisone or prednisolone is started in a dosage of 2 mg/kg/day. The total daily dose is usually split into two doses and given daily for four to eight weeks. Maintenance therapy should be tailored to the individual patient, with gradual weaning from glucocorticoid.

Patients with nephrotic syndrome are at high risk for infection and immunosuppression as a result of steroid therapy, which increases this risk. If the patient becomes febrile, blood and urine cultures should be obtained. If an infection is present, it should be promptly treated with an appropriate antibiotic.

Diuretic therapy may be beneficial, especially in patients with symptomatic edema. A loop diuretic, such as furosemide, may be given orally 91-2 mg/kg/day). Patients should be carefully observed for hypovolemic shock. If the edema is severe enough to warrant IV therapy, then salt-poor albumin should be infused concurrently. The usual dose is 1 g/kg given intravenously over two to four hours. Pneumococcal vaccine is indicated in all patients after remission is obtained

References:

Agraharkar, M. (2004), Nephrotic Syndrome. Retrieved June 29, 2009, from http://www.emedicine.com.

Travis, L. (2005). Nephrotic Syndrome. Retrieved June 29, 2009, from http://www.emedicine.com.