D4 entry on Guideslines/ Moratality rate* Nephrotic Syndrome

Zano/Balajadia Entry on Guidelines/Mortality rate of Nephrotic Syndrome

Corticosteroid therapy for nephrotic syndrome in children

In nephrotic syndrome (NS) protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised edema. While the majority of children with NS respond to corticosteroids, 70% experience a relapsing course. Corticosteroids have reduced the mortality rate to around 3%. However corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus and osteoporosis. The objectives were to determine the benefits and harms of corticosteroid regimens in preventing relapse in children with steroid sensitive NS (SSNS).We searched CENTRAL, Cochrane Renal Group Specialized Register, MEDLINE and EMBASE without language restriction, reference lists of articles and contact with known investigators. Randomised controlled trials performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent, with outcome data at six months or more. Two authors independently assessed trial quality and extracted data. Results were expressed as risk ratio (RR) with 95% confidence intervals (CI) or mean difference (MD). Meta-regression was used to explore potential between-study differences due to baseline risk of relapse, study quality and interventions.

Twenty four trials were identified. Six trials comparing two months of prednisone or prednisolone with three months or more in the first episode showed longer duration significantly reduced the risk of relapse at 12 to 24 months (RR 0.70, 95% CI 0.58 to 0.84). There was an inverse linear relationship between treatment duration and risk of relapse (RR = 1.26 - 0.112 duration; P = 0.03). Four trials showed that six months of prednisone was more effective than three months in reducing the risk for relapse (RR 0.57; 95% CI 0.45 to 0.71). Deflazacort was significantly more effective in maintaining remission than prednisone in children who frequently relapsed in a single study (RR 0.44, 95% CI 0.25 to 0.78). There were no increases in adverse events.

The result of the study proved that the children in their first episode of SSNS should be treated for at least three months with an increase in benefit for up to seven months of treatment. For a baseline risk for relapse following the first episode of 60% with two months of therapy, daily prednisone or prednisolone given for four weeks followed by alternate-day therapy for six months would reduce the number of children relapsing by 33%.

Hodson Elisabeth M,Willis Narelle S,Craig Jonathan C. NHS Evidence - kidney diseases formerly a Specialist Library of the National Library for Health. Systematic Review. 17 Oct 2007

Clinicopathological features and prognosis of Chinese children with
idiopathic nephrotic syndrome between different age groups

Jei-Wen Chang & Hsin-Lin Tsai & Hsin-Hui Wang & Ling-Yu Yang

Received: 17 September 2008 / Accepted: 3 December 2008 # Springer-Verlag 2008

Ethnicity and age play important roles in the epidemiology of idiopathic nephrotic syndrome (INS) in children. The purposes of this study were to compare the clinical features, renal histopathology, steroid response, and long-term prognosis in Chinese children between different age groups.

This is a retrospective cohort study of children aged between 2 and 18 years old with INS. Patients were divided into two groups according to age. Group I consisted of children between 2 and 8 years old (n =49). Group II consisted of the remaining patients (n =50). The clinical biochemical parameters, response to steroid treatment, renal histology, and long-term outcomes were analyzed. The biochemical parameters at the onset were similar in the two groups. Group II had a significantly higher frequency of microscopic hematuria (P= 0.011). Of the 67 children biopsied, minimal change disease was the most common histopathology for both groups. There was a higher frequency with focal and segmental glomerulosclerosis in group II (24% vs. 6.1%), but the difference between the two groups was not significant. During follow-up, the frequency of hypertension was significantly higher in group II (P=0.006). Two cases in group I developed chronic kidney disease (CKD) vs. eight cases in group II.
The frequency of progression to CKD is significantly higher (P=0.042) in Group II. In conclusion, children beyond 8 years of age with INS have a higher incidence of microscopic hematuria, higher risk of hypertension and progression to CKD in long-term follow-up.

Reference ：
http://www.springerlink.com/content/u6044122kr7457m3/

Prevalence and prognostic significance of malnutrition in chronic renal insufficiency.
Lawson JA; Lazarus R; Kelly JJ

A significant percentage of patients commencing dialysis do have manifestations of malnutrition. However, the prognostic significance as well as the prevalence significance of malnutrition with clients with Nephrotic syndrome before the start of dialysis therapy was poorly defined. This research is done in order to study whether there is a significance of malnutrition in an unselected group of patients having chronic renal failure. This study will utilize a cohort analytic study performed in an ambulatory care division of a university teaching hospital. Fifty patients with chronic renal failure were included in the study. The patients underwent nutritional assessment consisting of BMI measurement, midarm circumference, serum albumin concentration, total lymphocyte count and bioelectrical impedance analysis. The clients did receive standard medical care and subsequently followed-up at quarterly intervals for 12 months.

Results of the study revealed that the baseline data collected revealed 28% of the patients manifested malnutrition by SGA criteria. The patients with evident malnutrition had a significantly lower creatinine clearance, glomerular filtration rate, BMI, and MAC. But in terms of the serum albumin concentrations and total lymphocyte count, there were no significant differences in the laboratory values. At the end of the 12-month follow-up,there was a significantly increased mortality, composite endpoint of death or dialysis, and likelihood of acute hospitalization among the malnourished group. It is therefore concluded that there is a significant association between the baseline nutritional status and subsequent hospital admission to the baseline glomerular filtration rate and progression to ESRD.

The research study revealed that the data gathered from SGA provides a practical method of assessing the nutritional status and is useful in determining patients with increased risk of morbidity and mortality in the context of chronic renal failure.

References:
Data taken from: Journal of Renal Nutrition (J RENAL NUTR), 2001 Jan; 11(1): 16-22 (31 ref)

Authors and disclosures:
Research Assistant, University of New South Wales, Dept of Medicine, St George Hospital, Sydney, Australia

Response: FOLLOW-UP GUIDELINES AND MORTALITY
By: D2-Gil Legarda and Joanalyn Balino

High plasma phosphate as a risk factor for decline in renal function
and mortality in pre-dialysis patients

Nora Voormolen , Marlies Noordzij, Diana C. Grootendorst, Ivo Beetz, Yvo W. Sijpkens,Jeannette G. van Manen, Elisabeth W. Boeschoten, Roel M. Huisman, Raymond T. Krediet, Friedo W. Dekker, and the PREPARE study group

Voormolen, N. et al. made a retrospective follow-up study that aimed to assess the relationship of plasma phosphate with decline in renal function in incident pre-dialysis patient and its association with mortality. A total of 448 patients (1999-2001) included in the study. Inclusion criteria were: (1) with chronic kidney disease (CKD) stage IV–V; (2) availability of serum phosphate levels at the start of pre-dialysis; (3)renal replacement therapy (RRT) was expected within 1 year; (4) with estimated glomerular filtration rate (eGFR) of <20 ml/min/1.73 m; and (5)at least two measurements of serum creatinine during pre-dialysis care. Exclusion criteria include patients who spent less than 1 month on pre-dialysis care and with prior RRT.

The mean plasma phosphate concentration was 4.71 mg/dl. Plasma phosphate level was associated with baseline eGFR (ß –2.09, P<0.001).Higher plasma phosphate was associated with higher parathyroid hormone ( PTH), more proteinuria, younger age and the presence of glomerulonephritis or polycystic kidneydisease P<0.01. gender, hemoglobin concentration, nPNA and calcium were not associated with phosphate level after correction for baseline eGFR P >0.10. Plasma phosphate was also associated with decline in renal function. There were some patients who had an improvement in renal function during the pre-dialysis care period. PTH level was no association with the decline in renal function. 30 out of 448 patients died during pre-dialysis care. The overall mortality risk during pre-dialysis care for each increase of phosphate level with 1 mg/dl was 95% CI: 0.85–1.84.

High plasma phosphate level was identified as a risk factor for more rapid decline in renal function and was clearly associated with an increased mortality risk. The study revealed that hyperphosphataemia in pre-dialysis patients is not only a risk factor for higher mortality, but also for increased decline in renal function. It is important to importance on the plasma phosphate concentrations and make sure that it is within the normal range in pre-dialysis patients to maintain good renal function and prevent mortality.

Reference
Voormolen, N. et al(2007). High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 22: 2909–2916. Retrieved July 7, 2009 from
http://ndt.oxfordjournals.org/cgi/reprint/22/10/2909

Dyad Three (3)
Byron Webb A. Romero
Von Deneb H. Vitto
Raymond C. Ursal

Long-Term Outcome After Cyclophosphamide Treatment in Children With Steroid-Dependent and Frequently Relapsing Minimal Change Nephrotic Syndrome

Henriette A.C. Kyrieleis, MD,1 Elena N. Levtchenko, MD, PhD,1 and Jack F.M. Wetzels, MD, PhD2

The articles talks about the effects of long term cyclophosphamide treatment children under steroid dependent and frequent relapsing minimal change nephritic syndrome. Minimal change nephrotic syndrome (MCNS) is the most common cause of nephritic syndrome (NS) in children, accounting for 77% of cases according to the International Study of Kidney Diseases in Children. MCNS is a steroid-sensitive disease with a favorable long-term prognosis approximately 70% of children develops a steroid-dependent or frequently relapsing course of the disease.

From the pathology registry, 103 patients with biopsy proven MCNS received cyclophosphamide therapy. Ten patients were not treated with cyclophosphamide. Thus, we included 93 patients (64 males, 29 females) in our analysis. Median age at onset of NS was 3 years (range, 1 to 14 years), and median time of follow-up after onset of NS was 8 years (range, 1 to 39 years). Maximum follow-up of the disease in individual patients exceeded the period of 32 years from 1971 to 2003 because in some patients, cyclophosphamide was administered only after several years of relapsing disease.

The data shows that more than 25% of cyclophosphamide treated patients with childhood onset MCNS need medical therapy in adulthood. And quarter of a selected group of cyclophosphamide treated patients with steroid-dependent or frequently relapsing MCNS was not in remission after puberty and required prolonged immunosuppressive treatment. There is an urgent need for more effective treatment modalities resulting in persistent remission in these patients.

Reference:

Choudhry S. et. al. (2009) Long-Term Outcome After Cyclophosphamide Treatment in Children With Steroid-Dependent and Frequently Relapsing Minimal Change Nephrotic Syndrome 53(5): 760-9. Retrieved July 10, 2009 from MD consult http://www.mdconsult.com/das/article/body/148628844-13/jorg=journal&source=MI&sp=19489458&sid=860863133/N/581100/s0272638607005173.pdf?SEQNO=5&issn=0272-6386