Nephrotic Syndrome

D4 entry on Clinical Pathology, Epidemiology of Primary Nephrotic syndrome

Zaño, Alex
Balajadia, Bond

Primary or idiopathic Nephrotic syndrome is a collective term that describe the clinical picture of nephritic syndrome occurring in the absence of systemic disease, with an annual incidence of approximately 1-2 new cases per 100.000 population under the age of 16 years, The research entitled : Primary Nephrotic Syndrome – Mesangial Proliferative Glomerulonephritis In Childre: Clinicopathology and Treatment Outcome. This was a restrospective cohort study. A total of 117 patients with idiopathic syndrome biopsy proven masangial proloferative glumerulonephritis were seen at the Department of Pediatric Nephrology. National Kidney and Transplant Institute from January 1998 to December 2002. This was conducted to analize the clinic pathologic features and treatment outcome of the children with primary nephrotic syndrome biopsy confirmed mesagial proliferative glumerulonephritis. A retrospective analysis was carried out on all patients fulfilling the International Study of Kidney Disease in Children (ISKDC) criteria with onset between 1 and 16 years of age. Medical charts of patients were reviewed. Data gathered were clinical features, biochemical parameters, light and immunofluorescence microscopy co-morbities and treatment outcome (remmision, frequent relapse and no remission).

The study subjects were predominantly males with mean age of onset 5.4 years. Less than 10% of the children had hypertension. Hematuria was observed in more than half of the population. The results of the baseline biochemical tests of all the patients showed hypoproteinemia (mean+0.9 gm/dl SD 0.5) and hypercholesterolemia (mean = 518 ng/dl SD= 134). All the serum creatinine were normal with the mean of 0.6 mg/dl (SD=17). Presence of anti-human IgG, IgM and fibrinogen were often seen among the frequent relapsers with the positive rates of 65.96%, 54.24% and 65.31% respectively. However, there is no sufficient evidence to show that the presence of these immunofluorescence findings was more common among the said group (p-value=0.157, p=0.3135 and 0.157 respectively). Upper repiratory tract infection was the most common co-morbidity with an average occurrence of 6 (SD=2.93).

The study has provided a great deal of knowledge and significance on nursing care of patients with primary nephritic syndrome. The study reiterated the different treatment response and outcome that widens the prospect of treating the disease and adds on the development of nursing care plan for nephrotic syndrome. The histopathologic finding has been carefully studied to establish the features of nephrotic syndrome. As a result, much caution should be considered and implemented such as protecting the patient, prevent and limit exposure to subject of respiratory tract infection as the frequent relapse was the most prevalent outcome. On the other hand, its good thing to know though, that despite the severity and complexity of the disease, there are still children who has complete remissions with their treatment of the disease and able to live a normal life.

Reference: Valderrama et al. Primary Nephrotic Syndrome-Mesangial. NKTI Proceedings 6. July 2004

A research done by Abbas Ali Mansour, MD (2006) on the “significance of tubulointerstitial leasions in kidney biopsy of Nephrotic Patients in Iraq”, provides additional information in the diagnosis of Nephrotic Syndrome in general.

The study was done to give helpful information in approximating the severity and prognosis of Primary nephritic syndrome by examining biopsy specimen of patients with renal complaints. In the study, tubulointerstitial lesions (TIL) will be evaluated on its significance to affect the prognosis of Nephrotic syndrome. A clinical study was done to 136 patients with idiopathic nephrotic syndrome from Al-Rasheed Military Hospital in Baghdad Iraq. The patients were evaluated from the diagnosis until the follow-up treatments. The participants will be assessed for biopsy to look for histopathologic changes in the renal tubules of the kidneys. From the research done by Whermann (1990), usually interstitial fibrosis and tubular atrophy were used to evaluate prognosis of Glumerulonephritis. The same test will be evaluated for Nephrotic syndrome since few research literatures provides information with regards to its reliability. Use of Chi-square was utilized for statistical analysis of the data and a P value of < .05 was considered to be significant for the study.

The results revealed that TIL can adversely affect the prognosis of chronic progressive glumerulonephritis. TIL can be considered significant in estimating nephron injuries from the samples taken from renal tissue biopsy. Indexes from TIL should always be considered in diagnosing nephrotic syndrome and not only on glomerular and vascular changes in the renal tubules. TIL from the time of biopsy can present the only significant morphologic parameter that can be used to predict whether the disease will follow a favorable course, even in the same type of GN

Response by:
Joanalyn S. Balino and Gil Legarda

Title: Repetitive Fragmentation Products of Albumin and
α1-Antitrypsin in Glomerular Diseases Associated with
Nephrotic Syndrome

Giovanni Candiano,* Luca Musante,*† Maurizio Bruschi,*† Andrea Petretto,‡
Laura Santucci,*† Piero Del Boccio,§_¶ Barbara Pavone,§_¶ Francesco Perfumo,**
Andrea Urbani,§_¶ Francesco Scolari,†† and Gian Marco Ghiggeri*

Research Appraisal

There were 23 participants involved in the study. These patients have nephrotic syndrome and have different pathologic backgrounds. Clinical data and renal histology are the basis of diagnosis. The criteria were there should be a presence of nephrotic syndrome (proteinuria >40 mg/h per m2) with onset at <16 yr of age and in cases of steroid dependence and/or resistance, availability of a renal biopsy; there is absence of familial traits of nephrotic syndrome and/or relevant mutations of slit-diaphragm genes (NPHS2, CD2AP, and ACTN4) ;and a presence of nephrotic syndrome at any age with MGN.

Albumin fragments account for 25 to 30% of total albumin in urine of nephrotic patients while their proportion in serum does not exceed 5%. There are almost 30 g of fragments is cleared monthly from plasma, accounting for 30% of the albumin pool in a patient who weighs 30 kg considering that in nephrotic syndrome at least 2 to 3 g of albumin is lost every day in urine and that up to 1 g (30%) is represented by fragments.

Albumin fragments in nephrotic urine high concentration suggests a preferential urinary excretion and it reflects the partial maintenance of size selectivity properties of the kidney.Preferential urinary excretion of albumin fragments in nephrotic patients represents an efficient depurative mechanism that restores normal albumin composition in plasma, and similar considerations can be relate to a1AT.

Reference
Candiano et al. (2006). Repetitive Fragmentation Products of Albumin and α1-Antitrypsin in Glomerular Diseases Associated with Nephrotic Syndrome. J Am Soc Nephrol 17: 3139-3148. Retrieved June 21, 2009 from http://jasn.asnjournals.org/cgi/reprint/17/11/3139?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&minscore=5000&resourcetype=HWCIT

Dyad 3:
Byron Webb A. Romero
Von Deneb H. Vitto
Raymond C. Ursal
Etiology and Clinical Characteristics of Membranous Nephropathy in Chinese Patients
Cai-Hong Zeng, PhD, Hui-mei Chen, PhD, Rui-Shi Wang, MD, Yan Chen, MD, Su-Hua Zhang, MD, Li Liu, MD, Lei-Shi Li, MD, and Zhi-Hong Liu, MD
Membranous nephropathy (MN) is a common cause of proteinuria and can be subdivided into idiopathic and secondary classifications. Most patients with MN present with associated systemic diseases that need to be identified before appropriately diagnosing idiopathic MN.
This report is the first large retrospective study of eastern Chinese patients with MN. Secondary MN was more common in Chinese patients with MN, and its incidence was significantly greater than those reported from other developed countries. First, the understanding and diagnosis of MN have improved greatly in recent years, and more secondary causes of MN had been identified. Second, indications for renal biopsy in the study may be different than those in other countries obtained in the 1970s and 1980s. Third, patients with pure MN (light and electron microscopy evaluation) and glomerular C4 and/or C1q deposition (except for IgG and C3 by means of immunofluorescent staining) with no identified secondary cause were excluded from the study. Fourth, most physicians hesitate to perform renal biopsies in patients with systemic diseases (eg, autoimmune diseases) in developed countries. However, SLE is a major secondary glomerular disease in our institute that has been diagnosed in 1,352 patients. Because of the mentioned reasons, SLE and HBVinfection were the leading secondary causes of MN in Chinese patients.
Proteinuria was a common presentation in patients with idiopathic MN, which was predominately found in middle-aged to elderly men. Secondary MN was more common than idiopathic MN, and most secondary MN diagnoses were secondary to systemic lupus erythematosus and hepatitis B infection.
Reference:
Etiology and clinical characteristics of membranous nephropathy in Chinese patients American Journal of Kidney Diseases - Volume 52, Issue 4 (October 2008) http://www.mdconsult.com/das/article/body/1448073486/jorg=journal&source=MI&sp=21012194&sid=854675134/N/662949/s0272638608010585.pdf

response by
Yang ChunHua and Yuan ShuHui


Minimal Change Nephrotic Syndrome: A Genetic Variant

Introduction: Minimal change nephrotic syndrome (MCNS) is the most common form
of nephrotic syndrome in children, a disorder affecting the glomeruli of the kidney. This
case describes a toddler with steroid-resistant MCNS, appearing to be a familial trait.

Methods: The child was examined with parental consent. No study was necessary and
no institution review was obtained due to the nature of the report.

Results: A 15 month old male presents with 2 week history of facial and orbital swelling,
progressing to shifting edema between the face and lower extremities. He was noted to
have proteinuria, hematuria, and an albumin of 1.4. The patient was admitted to establish
a therapeutic regimen with the diagnosis of nephrotic syndrome. During his admission,
he was treated with prednisolone and multiple albumin/lasix infusions with minimal
resolution of his edema. After becoming stable, he was discharged with close follow up
with a pediatric nephrologist. After 4 weeks of minimal response to steroids, a renal
biopsy was done showing, !°moderate amount ofeffacement of epithelial foot processes
and focal slight mesangial sclerosis,!± indcating a likely diagnosis of minimal change
disease. There is a family history of minimal change disease: the patient!ˉs mother and
maternal uncle. They were both diagnosed by renal biopsy at age 3 and did not resolve
until age 15, but their disease show steroid sensitivity. The maternal grandparents are
first cousins and showed no signs of nephrotic syndrome.

Conclusions: Minimal change nephrotic syndrome is a common disease in children, but
rarely shows a clear familial lineage. There is an autosomal dominant transmission of
ACTN4 and an autosomal recessive transmission of NPHS2, each can cause nephrotic
syndrome. This patient!ˉs family history nd disease course, however, does not seem to
fit in clearly to any of these currently known genetic forms of nephrotic syndrome.
Further research is being performed to detect a possible genetic link for this patient.

Nephrotic Syndrome
Nephrotic syndrome (nephrosis ) is not a single disease but a group of symptoms. Symptoms include heavy proteinuria, hypoalbuminemia, edema, hypercholesterolemia, and normal renal function. Nephritic syndrome can be primary or secondary. Primary nephritic syndrome occurs as part of a recognized systemic disease.

Epidemiology
Nephrotic syndrome is often described a disease of children and is relatively rare. It is 15 times more common in children than in adults. The reported annual rate is 2 to 5 per 100,000 children younger than 16 years. The cumulative prevalence rate is approximately 15.5 per 100,000 individuals according to Travis (2005). Nephritic syndrome prevalence is difficult to establish in adults because the condition is usually a result of an underlying disease. In adults, diabetes mellitus is emerging as a major cause of nephrotic syndrome, thus American Indians, Hispanic (Americans), and African Americans have a higher incidence of nephrotic syndrome compared to Caucasians (Agraharkar, 2004).

Pathophysiology
Nephritic syndrome results from damage to the kidneys’ glomeruli, the tiny blood vessels that filter waste and excess water from the blood and send them to the bladder as urine. They consist of capillaries that are fenestrated, that is, have small openings, which allow fluid, salts, and other small solutes to flow through but normally not proteins. Damage to the glomeruli from diabetes, glomerulonephritis, or even prolonged hypertension, causes the membrane to become more porous, so that small proteins, such as albumin, pass through the kidneys into urine. As proteins continue to be excreted, serum albumin is decreased, which in turn decreases serum osmotic pressure. Capillary hydrostatic fluid pressure becomes greater than capillary osmotic pressure, which results in generalized edema. As fluid is lost into the tissues, the plasma volume decreases, stimulating secretion of aldosterone to retain sodium and water, which decreases the glomerular filtration rate to retain water. This additional water also passes out of the capillaries into the tissue, leading to greater edema.

Assessment with Clinical Manifestations
The major clinical manifestation is edema, which is the presenting symptom in about 95% of cases. In adults, edema is usually present in dependent parts, such as ankles or legs, and is pitting in nature. In children, periorbital edema edema is common. Patients may have fluid in the pleural cavity, causing pleaural effusion, or in the abdominal area, causing ascites. The edema may progress rapidly or quite slowly. Eventually, the edema is present throughout the body, which is known as anasarca. Some patients may even notice foamy urine, due to a lowering of the specific gravity by the high amount of proteinuria. Actual symptoms may include anorexia, irritability, fatigue, abdominal discomfort, and diarrhea (Travis, 2005).
When taking a history, many patients report a viral upper respiratory tract infection immediately preceding the first clinical signs of the disease but its relevance to the nephrotic syndrome is unknown. A history of prior allergic events is common. Children should be questioned about insect stings, immunizations, or poison ivy. In adults, it is important to ask about underlying diseases that may be the cause of nephrotic syndrome.

Diagnostic Tests
Laboratory tests include a urinalysis for protein and cellular elements and serum tests for protein and lipid analysis. Protein in the urine usually exceeds 100 mg/dL abd values as high as 1000 mg/ L are common. Protein can also be tested with a dipstick and may be as high as +3 to +4. The protein-to-creatinine ratio may vary from 1 to 20 (normal is less than 0.2). Hematuria also may or may not be present. Hypoalbuminemia is common, with serum albumin levels following below 2 g/ dL. Lab values as low as 0.5 g/ dL are not uncommon. Hyperlipidemia is common and typically correlates inversely with the concentration of serum albumin. Values for lipids may remain moderately elevated for one to three months after remission of proteinuria (Daniels, 2003).

References:

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

Daniels, R. (2003). Delmar’s Manual of Laboratory and Diagnostic Tests. New York: Thomson Delmar Learning.

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