Epidemiology and Pathophysiology of Glomerulonephritis

Dyad 3:
Byron Webb A. Romero
Von Deneb H. Vitto
Raymond C. Ursal

Glomerulonephritis (GN) is a disease condition where immunologic mechanisms trigger inflammation of the glomerulus as well as the proliferation of glomerular tissue resulting into basement membrane, mesangium, and capillary endothelium damage (Papanagnou, 2008). Etiologies may vary, however, majority of the cases are idiopathic while one of the known causes of GN include infection (such as that of streptococcal infection [Pais, Kump, & Greenbaum, 2008]). Because of this, clinical manifestations of patients with GN include hematuria, proteinuria and RBC casts which may be accompanied by azotemia, oliguria, and decreased GFR (glomerular filtration rate). For definitive diagnosis, Renal Biopsy is required as it is also used to diagnose several renal problems (Papanagnou, 2008; & Fuiano, et. al, 2001). Patients who are candidates for renal biopsy are those with individual, or familial history of renal disease, as well as patients with atypical presentation (includes proteinuria, nephritic syndrome, or a rapid rise in the level of creatinine without resolution). Fuiano, et.al (2001), mentioned that when patients are presenting with signs and symptoms of renal insufficiency, renal biopsy establishes a pathologic diagnosis. Certain considerations are however taken into account such as the kidney size or the extent of kidney insufficiency prior to undergoing a renal biopsy. As for patients with severe chronic insufficiency, undergoing this procedure poses additional complications and seems futile as this would not effect management of the condition. But for mild to moderate renal insufficiency, the procedure may identify the causes of the problem and may alter the treatment course. For acute renal insufficiency, biopsy still remains important. IgA nephropathy (IgAN) was the most common glomerulonephritis at renal biopsy in a study conducted by Coppo, Gianoglio, Porcellini, and Maringhini (1998). As createnine concentration is the most common biomarker to predict the level of GFR (in effect, kidney function), it is used therefore to determine the severity of the disease condition. Obrenovic, et.al (2006) highlighted in there research study that there are certain limitations that interfere with the result of using createnine as biomarker. Factors include age, gender, muscle mass, diet, and drug use. In the same experimental study, the researchers explored on the relationship of proteinuria on crystatin C concentration in patients with GN. Lhee, et.al (2006) conducted a study on whether Neopterin can serve as an indicator of the disease activity and as a prognostic measure same as other clinical parameters including BUN, createnine levels and serum albumin). Neopterin is a serum and urine marker produced by guanosine triphosphate (GTP), and is synthesized by the macrophages and when T cells are active during immunologic processes.

In GN, there are more males acquiring the condition with a ratio of 2:1. This particularly afflicts children and young adolescents, (5-15 years of age) while a smaller portion, 10% occur in patients above 40 years. It may however be acquired at any time in the lifespan. Statistics of GN in the United States would reveal that of the glomerular disease, there is 10-15% representation of GN. (Papanagnou, 2008). Immunoglobulin A (IgA) nephropathy GN is the most common cause of GN worldwide. While there had been reduction in the incidence of poststreptococal GN in majority of western countries, it remains much more common in regions such as Africa, the Caribbean, India, Pakistan, Malaysia, Papua New Guinea, and South America.

Because assessment is the first phase and is of basic importance in the nursing process, researches related to assessment of patients with GN have direct impact on the care provided by nurses. Baseline data are further strengthened by such researches as above and provides a clearer understanding of the case scenario and that of the pathophysiologic process of GN. It is therefore imperative for nurses to update themselves regarding updates brought about by scholarly made researches and evidence-based researches.

References:

Coppo, R., Gianoglio, B., Porcellini, M.G., & Maringihi, S. (1998). Frequency of renal diseases and clinical indications for renal biopsy in children (Report of the Italian National Registry of Renal Biopsies in Children. Nephrology Dialysis Transplantation. 13: 294-297. Retrieved June 19, 2009, from http://ndt.oxfordjourbals.org/cgi/reprint/13/2/291

Fuiano, G., Mancuso, D., Comi N., Mazza, G., & Fabiano, G. (2001). Renal Biopsy: Clinical Indications. Italy: Chai of Nephrology. Retrieved June 18, 2009 from http://www.unimet.edu/cin2001-old/conf/fuiano.html

Papanagnou, D. (2008). Acute Glomerulonephritis. Retrieved on June 18, 2009, from
http://emedicine.medscape.com/article/777272-overview

Pais, P.J., Kump, T., & Greenbaum, L.A. (2008). Delay in Diagnosis of Poststreptococcal Glomerulonephritis. Journal of Pediatrics. 154 (4). Retrieved June 19, 2009, from http://www.mdconsult.com/das/article/body/144255924-4/jorg=journal&source=MI&sp=21362908&sid=854139863/N/662460/1.html?issn=0022-3476

In addition, we would like to add a research that discusses one of the causes of Progressive glomerulonephritis which is Pauci-immune crescentic glomerulonephritis (CrGN).

Title:
Antineutrophil Cytoplasmic Autoantibody–Negative Pauci-immune Crescentic Glomerulonephritis
Min Chen, Feng Yu, Su-Xia Wang, Wan-Zhong Zou, Ming-Hui Zhao and Hai-Yan Wang

Research Appraisal

A retrospective study was used by the researchers in order to analyze the characteristics of patients with CrGN with negative Antineutrophil cytoplasmic autoantibody (ANCA).One of the causes of Progressive glomerulonephritis is Pauci-immune crescentic glomerulonephritis (CrGN). A serologic marker for primary systemic small vessel vasculitis was ANCA. The researchers investigated the clinical and pathologic characteristics of patients with ANCA-negative pauci-immune CrGN, and they made a detailed comparison between patients with ANCA-negative and ANCA-positive pauci-immune CrGN. 85 patients from in the Renal Division and Institute of Nephrology, Peking University First Hospital whose pauci-immune CrGN was diagnosed from 1997-2006 participated in this study. Patients who were exluded are with those with secondary vasculitis or with anti–glomerular basement membrane antibodies. T-test was used in assessing the differenced of quatitative parameters between groups for normally distributed data. Mann-Whitney U test was used in testing the differences of semiquantitive results. X 2 for comparing the differences in qualitative results. Kaplan-Meier curves for the analysis of patient survival and renal survival.

Results: 28 out of 85 patients with pauci-immune CrGN were ANCA negative. Those were younger that ANCA positive (P<0.001). There is pooper renal survival in ANCA- negative patients (P<0.05). The prevalence of nephrotic syndrome and level of urinary protein were higher in ANCA-negative patients. On the other hand, ANCA-negative patients have lower prevalence of extrarenal involvement.


Reviewer’s Conclusion: Patients with negative ANCA constituted a minority of patients with pauci-immune CrGN with the results that ANCA-negative patients had poorer renal outcome, high prevalence of nephritic syndrome and level of urinary protein ANCA -positive pauci-immune CrGN might represent an independent disease entity.


Reference
Chen,Min et al (2007). Antineutrophil Cytoplasmic Autoantibody–Negative Pauci-immune Crescentic Glomerulonephritis. J Am Soc Nephrol 18: 599-605, Retrieved June 21, 2009 From: http://jasn.asnjournals.org/cgi/reprint/18/2/599?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=glomerulonephritis+causes&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Urine Proteomics for the Early Diagnosis of Acute Glomerulonephritis: Has the
Time Come?
Dimitrios T. Boumpas and Takashi Kuroiwa.
Vol. 56, No. 3, March 2007, pp 705–709
DOI 10.1002/art.22413
2007, American College of Rheumatology

An evidence based study conducted prooves that all forms of glomerulo nephritis are immune mediated. From the antibodies infiltrating the kidneys, moslty neurtophils and macrophages cause direct renal damage. Since injury can cause tissue damage, presence of protein in the urine may indicate renal damage. It also reflects the function of the glomerular apparatus, the tubules and collecting ducts. The gerated polypeptide in the urine provides a signature of a particuar pathologic process. Such changes detected may offer potential primary or secondary diagnosis or renal damage. A Sudy conducted by Wu (2007), provides evidences of the important contribution of biomakers for glomerulonephritis.

There are limitaions seen in the study. First, the appearance of protein molecules in the urine might indicate other diseases whose manifestations were microalbuminuria. The test in detecting specific protein for glomeruloneprhitis should be more sensitive for acurate measurements. Second, detection of the biomakers does not specifically determine the severityt of the disease which inturn may lead to lag in the treatments and overutilization of renal biopsy for diagnosis. Lastly, the clients participating in the study might be receiving medications such as corticosteroid and ace inhibitor which may affect the production and excretion of protein in the urine, thus affecting the results of the study.

We recommend that the utilization of protein as a biomaker for glomerulonephritis may be studied further. The researchers should consider the specificity of the diagnostic exam to glomerulonephritis. Providing advancement research for the early diagnosis of GN should benefit the clients by providing information on the degree of the disease so that prompt treatmemt will be utilized and provide greater chances for the client's recovery.

references:
Wu T, Xie C, Bhaskarabhatla M, Yan M, Leone A, Chen SS, et al.
Excreted urinary mediators in an animal model of experimental
immune nephritis with potential pathogenic significance. Arthritis
Rheum 2007;56:949–59.

Kuroiwa T, Lee EG. Cellular interactions in the pathogenesis of
lupus nephritis: the role of T cells and macrophages in the
amplification of the inflammatory process in the kidney. Lupus
1998;7:597–603.

Boumpas BT, Balow JE. Outcome criteria for lupus nephritis
trials: a critical overview. Lupus 1998;7:622–9.

Response by: Dyad 4: Zaño, Alexis/Balajadia, Bond

Additional info on Epidemiology of Glumerulonephritis

Recurrent Glomerulonephritis after Renal Transplantation: An Unsolved Problem

Recurrence of glomerulonephritis (GN) and the occurrence of new GN (de novo GN) in the transplanted kidney are not uncommon and have been reported since the early days of transplantation. There have been improvements in short- and long-term graft survival after renal transplantation in the past two decades. Development of new immunosuppressive medications has been targeted toward controlling acute and chronic rejections but has not influenced the occurrence and outcome of recurrent and de novo GN after renal transplantation. It is estimated that approximately 10 to 20% of patients with GN develop recurrence in the allograft and 50% of them lose their graft on long-term follow-up, thus having a negative impact on long-term graft survival.
Diagnosis and management of recurrence of native GN is critical to optimize and improve long-term kidney transplant graft survival and also provides a unique opportunity to explore the pathogenesis of native kidney disease. The goal for the 21st century should be to understand the pathogenesis of recurrent GN and to implement protocols for the prevention and treatment of recurrent GN, thus optimizing renal transplant outcome. This article illustrates clinical and histologic classifications of recurrent GN and analyzes the problems related to diagnosis of recurrent GN. In addition, epidemiology of native GN in patients with ESRD and recurrent GN after renal transplantation are discussed. This article includes a section on individual GN but does not address metabolic diseases such as diabetic nephropathy.

Despite advances in prevention of acute rejection and improved short- and long-term kidney graft survival, recurrent glomerulonephritis remains problematic and poorly characterized. This study analyzed prevalence and outcome of recurrent glomerulonephritis from various registries. Definition, classification, and limitations in evaluating epidemiology of native and recurrent glomerulonephritis are discussed. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. Analysis of data from transplant registries revealed that glomerulonephritis is an important cause of end-stage renal disease in white and pediatric recipients; however, glomerulonephritis as the cause of end-stage renal disease is not characterized well in black recipients, and many of them are perhaps labeled to have hypertensive nephrosclerosis as the cause of renal disease without renal biopsy. A systematic approach toward urinalysis after transplantation and utility of immunofluorescence and electron microscopic examination of renal biopsy tissues will identify the true prevalence of recurrent glomerulonephritis. Data on recurrent glomerulonephritis should be compiled by either using registry analysis or pooling data from multiple centers. This will provide true data on prevalence and outcome and could potentially initiate translational research studies.

The understanding of the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as to treat individual recurrent glomerulonephritis, which can enhance long-term graft survival.

With the research presented above, the nursing profession will benefit from this study by utilizing the results in making a comprehensive care of plan for patients who posses Glumerulonephritis. The plan will focus on permanently stop or prevent the recurrence of the said condition. Its alarming to know though, that despite the efforts of the researchers to find a cure or a proper management of this condition, recurrence still occur due to the fact that there has been limited advance in the area of recurrent GN.

Reference: Golgert, William A et. al.Recurrent Glomerulonephritis after Renal Transplantation: An Unsolved Problem. PMC. January 2 2008

Glomerulonephritis is a type of kidney disease that involves the glomeruli. The glomeruli are very small, important structures in the kidneys that supply blood flow to the small units in the kidneys that filter urine, called the nephrons. During glomerulonephritis, the glomeruli become inflamed and impair the kidney's ability to filter urine.