Types of Nephritis
Depending to the locations of inflammation, Nephritis can be classified as follows
I. Glomerulonephritis
Glomerulonephritis is defined as the condition of inflammation of the tiny filters in kidneys (glomeruli), which filter blood by removing excess fluid, electrolytes and waste and pass them through urination.
1.. Acute Glomerulonephritis
A sudden onset of inflammation of glomeruli.
2. Chronic Glomerulonephritis
This is a graduated progression of kidney diseases. It can be primary or as a result of certain diseases
II. Interstitial nephritis (Tubulo-interstitial nephritis)
Interstitial nephritis is defined as a condition of inflammation of the spaces between renal tubules, affecting the interstitium of the kidneys and kidney function in wast removal.
1, Acute Interstitial nephritis
A sudden onset of the inflammation of the diseases
2. Chronic Interstitial nephritis
In most case, it ends in kidney failure
I. Glomerulonephritis
Glomerulonephritis is defined as the condition of inflammation of the tiny filters in kidneys (glomeruli), which filter blood by removing excess fluid, electrolytes and waste and pass them through urination.
A. Signs and Symptoms
A.1. Acute Glomerulonephritis
According to the study by Movchan EA, in the study of Evolutionary trends in symptoms of acute glomerulonephritis in adult population of the Novosibirsk region, indicated that AGN occurs not often but with stable rate. It is encountered more frequently in young men. The last decade is characterized by higher morbidity after streptococcal infection, high percentage of women at reproductive age, aggravation of the clinical course with marked edemas, severe arterial hypertension, renal dysfunction (acute renal failure in 10.4%), cases of left ventricular failure (5.2%) and eclampsia (1.7%) not registered earlier(1).
A.2. Chronic Glomerulonephritis
In the study of Incidence and characteristics of the hypertension syndrome in chronic glomerulonephritis, by Dr. Stefanov G. showed that in the random group, 65.1 per cent had renoparenchymal hypertension (RPH), 34.8 per cent of the patients had RPH among the patients with normal renal function, and with various degrees of chronic renal insufficiency (ChRI) - 95.4 per cent..... In 48 per cent but patients with ChGN without RPH also had the same complaints--26 per cent. Complaints as dizziness, tinnitus and insomnia were rare. The hypertension was with a short duration (according to anamnestic data)--in 2/3 less than three years and 40 per cent of the patients had hypertonic crises or/and acute left cardiac insufficiency in spite of the relatively little alterations in ECG and fundus of the eye(2).
3. Other symptoms include
a. Hematuria
Hematuria is condition of the presence of red blood cells in the urine.
There is a report of a a 16 year old male with a history of recurrent synpharyngitic macroscopic hematuria presented with severe loin pain, macroscopic hematuria and oliguric acute renal failure, according to the study by Dr. Kincaid-Smith P and the research team(3).
b. Proteinuria (The presence of an excess of proteins in the urine)
Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney(4)
c. Cold sweating, general fatigue, and somnolence
There is a report of a 66-year-old woman, who has been under hemodialysis due to antineutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis since 2003, was hospitalized because of cold sweating, general fatigue, and somnolence, According to the research team at the Divisions of Endocrinology and Metabolism(5).
B. Causes and Risk factors
B.1. Causes
1. Infections
In the study of Glomerulonephritis causing acute renal failure during the course of bacterial infections of of four male patients, aged 53-71 years, who developed GN and ARF following bacterial infections, showed that
a. The first two patients developed GN with immunoglobulin A (IgA) deposits after infections with hospital-acquired methicillin resistant Staphylococcus aureus (MRSA). Clinical, serologic and histological features, classification of GN and treatment differed between the two patients.
b. The third patient developed simultaneous acute rheumatic fever and post-streptococcal GN causing severe ARF requiring hemodialysis. Complete recovery of ARF and migratory polyarthritis followed initiation of corticosteroids.
c. The fourth patient developed ARF and cerebral vasculitis following a prolonged course of Streptococcus mutans endocarditis with delayed diagnosis. He also developed multiple serological abnormalities including elevated titers of antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), anti-phospholipid antibodies, rheumatoid factor, and modest hypocomplementemia(6).
2. Lupus
In the study of Distinct roles for complement in glomerulonephritis and atherosclerosis revealed in mice with a combination of lupus and hyperlipidemia by Dr. Lewis MJ and the research team at the Imperial College London showed that accelerated atherosclerosis and renal inflammation in SLE are closely linked via immune complex formation and systemic complement depletion. However, whereas hyperlipidemia will enhance renal immune complex-mediated complement activation and the development of nephritis, accelerated atherosclerosis is, instead, related to complement depletion and a reduction in the uptake of apoptotic/necrotic debris(7).
3. Goodpasture's disease
In the study of the Progression from Goodpasture's disease to membranous glomerulonephritis, according to the research team at the Department of Renal Medicine, Concord Hospital, Sydney, thwew is report of an unusual case of a patient with Goodpasture's disease presenting with hemoptysis, severe iron deficiency anemia and microscopic hematuria and proteinuria.... Nine months after presentation he developed nephrotic range proteinuria and a repeat renal biopsy revealed membranous glomerulonephritis with no evidence of his original disease(8).
4. IgA nephropathy
IgA nephropathy is an autoimmune disease, affecting the kidneys
IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23(9).
5. Polyarteritis nodosa (PAN)
Polyarteritis nodosa (PAN) is defined as a vasculitis of medium & small-sized arteries
There is a report of a 53-year-old man with hepatitis C virus (HCV) infection underwent cholecystectomy for presumed cholecystitis. Gallstones were not present, and histological examination demonstrated medium-sized arteritis, consistent with polyarteritis nodosa (PAN). The patient later developed rapidly progressive glomerulonephritis. Kidney biopsy demonstrated cryoglobulinemic glomerulonephritis(10).
6. Polyangiitis (Wegener's granulomatosis)
Polyangiitis is defined as a vasculitis of small-sized blood vessels. Granulomatosis with polyangiitis (GPA), is the recently proposed, new alternative name for Wegener's granulomatosis. It defines a systemic small-vessels vasculitis, characterized by frequent involvement of upper and lower respiratory tract. According to Dr. Karras A, and the research team at hôpital Européen Georges-Pompidou, service de néphrologie(11).
7. Other causes
a. Homozygous C1q deficiency
According to the study of in mice, Dr. Botto M and the research team at the Imperial College School of Medicine, indicated that among mice without glomerulonephritis, there were significantly greater numbers of glomerular apoptotic bodies in C1q-deficient mice compared with controls. The phenotype associated with C1q deficiency was modified by background genes. These findings are compatible with the hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells(12).
b. Deficiency of factor H
Factor H is a member of the regulators of complement activation family, a complement control protein. Factor H, the main regulator of this activation, prevents formation and promotes dissociation of the C3 convertase enzyme, and, together with factor I, mediates the proteolytic inactivation of C3b. Factor H deficiency, described in 29 individuals from 12 families and in pigs, allows unhindered activation of fluid-phase C3 and severe depletion of plasma C3 (ref. 11). Membranoproliferative glomerulonephritis (MPGN) occurs in factor H-deficient humans and pigs(13).
B.2. Risk factors
1. Age, hypertension, and presence of nephrotic range proteinuria
The risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors(14).
2. Hepatitis C virus (HCV)
People with the infection of hepatitis C virus (HCV) are at increased risk to develop glomerulonephritis(15).
3. Genetic passing through
Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome(16)
4. Diabetes
There is a report of an 88-year-old man with a 30-year history of type 2 diabetes and a 3-year history of chronic renal failure was admitted for evaluation of anasarca. On admission, findings of nephrotic syndrome and microscopic hematuria were observed. During the course of therapy, rapid deterioration of renal function occurred with the appearance of pneumonia. Irrespective of the therapy with hemodialysis and antibiotics, he died of respiratory failure. The autopsy showed a rare case of rapidly progressive glomerulonephritis (crescentic glomerulonephritis) superimposed on membranous nephropathy(17)
4. Other risk factors
History of cancer, Blood or lymphatic system disorders, Exposure to hydrocarbon solvents are associated to higher risk to develop glomerulonephritis(17)
C. Complications
1. Heart failure (HF), acute renal failure (ARF), hypertensive encephalopathy and nephrotic range proteinuria
In the study of Systemic complications of acute glomerulonephritis in Nigerian children, by Dr. Olowu WA at the Obafemi Awolowo University Teaching Hospitals Complex, showed that majority of the patients (18/29) were under 6 years of age, with peak age incidence of 3 years. The hospital incidence of AGN and prevalence of systemic complications were 10 new cases per year and 41.38%, respectively. Heart failure (HF) and acute renal failure (ARF) were sole systemic complications in 7 and 2 AGN patients, respectively. Three patients had double systemic complications: one each of hypertensive encephalopathy (HTE)+HF, HTE+ARF and ARF+HF. Ten of 29 patients (34.48%) had nephrotic range proteinuria. None of the AGN patients except those with ARF had FeNa >1%, plasma bicarbonate <15 mmol/l, urea 225 mmol/l and creatinine 2400 mmol/l. Two of the patients died: one each of ARF and ARF+HF, giving a case fatality and mortality rate of 6.90% and 0.08%(18).
2. Chronic kidney failure
In most cases of glomerulonephritis (GN), long-term course can lead to chronic renal failure(19).
3. Etc.
D. Diagnosis
After completing the physical exam and family history, the tests which your doctor orders include
1. Urinalysis
The aim of the test is to check
a. Damage to the glomeruli
If the test shows the presence of red blood cells and red cell in the urine.
b. Infection or inflammation
If the white blood cells are presented in the urine, in mmost case.
c. Nephron damage
If the presence of protein is found in the urinary test.
2. Blood tests
The aim of the test is to check for the presence of wast products which will provide the information of kidney damage and impairment of the glomeruli
3. Imaging tests
Image test such as an ultrasound examination or a computerized tomography (CT) scan will provide visualization of the the damage of the patient kidneys.
4. Kidney biopsy
The diagnosis of glomerulonephritis can be confirmed by performing a kidney biopsy. A small sample is extracted from the small pieces of kidney tissue for microscopic examination. The procedure is important in predicting the likely progress, response to treatment and outcome of glomerulonephritis.
In the analyzing whether histological diagnosis of glomerulonephritis (GN) at an early stage of chronic kidney disease (CKD) associated with different outcome and compared to diagnosis at a more advanced stage. Patients with CKD stage 1 and 2 at kidney biopsy had fewer endpoints compared to patients with a GFR of <60 ml/min (p < 0.001). Kidney function at the time point of histological glomerulonephritis (GN) diagnosis is associated with clinical outcome, likely due to early initiation of specific drug treatment. This suggests that selection of therapy yields greatest benefit before renal function is impaired in GN(20).
E. Prevention
E.1. The do`s and do not`s list
1. Diet to enhance your immune to prevent infection and inflammation caused by bacteria and virus, including HIV and hepatitis.
2. Mediterranean diet
On the most healthy diet in the Southern Italy and Northern Greek. MeDiet score was created based on the intake of ten food components: vegetables; whole grains; nuts; legumes; fruits; ratio of monounsaturated:saturated fat; red and processed meat; dairy products; fish; alcohol. researchers at the University of Minnesota, in the study of Relationships of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA), showed that ahigher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During the follow-up, 412 incident diabetes events accrued. The MeDiet was not significantly related to the risk of incident diabetes (P for trend = 0·64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori MeDiet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and with lower blood glucose before adjustment for obesity, but not with a lower incidence of diabetes(21).
3. Stop smoking
Cigarette contains many harmful chemicals, including cadmium. There is a significant association between blood cadmium levels and elevated blood pressure regardless of the type of variable (continuous or categorical) in women and men with a lower blood cadmium level compared to previous Korean studies, according to the study by the Soonchunhyang University(22),
4. Safe sex
Safe sex to prevent infection caused by sexual transmitting diseases.
5. Eat well to prevent fluctuation of insulin levels of that can increase the risk of diabetic nephropathy
6. Reduce intake of salt to prevent fluid retention, swelling and hypertension
7. Maintain healthy weight to prevent complications due to obesity
8. Etc.
E.2. Phytochemicals to prevent glomerulonephritis
1. (-)-epigallocatechin-3-gallate (EGCG)
In the study of Glomerulonephritis therapy: is there a role for green tea?, researchers at the Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, showed that (-)-epigallocatechin-3-gallate (EGCG) treatment ameliorates renal inflammation, tissue damage, and loss of renal function and might therefore represent a novel therapeutic approach for human glomerulonephritis(23).
2. Resveratrol
Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC(50) of 10 microM without inducing apoptosis(24).
3. Isoflavones genistein and genistin
In the study to evaluate the Male Wistar rats with glomerulonephritis caused by a single intravenous injection of nephrotoxic serum,with 5 mg of genistein or 8 mg of genistin/d/100 g body weight for 12 d given orrally, found that these isoflavones suppressed nephritis-induced severe hypercholesterolemia and hypertriglyceridemia, and their hypolipidemic action was almost identical. Fecal steroid excretion was unchanged by administration of the two isoflavones. Genistein inhibited the incorporation of [1-14C]acetate into cholesterol and FA in liver slices from nephritic rats when added to an incubation buffer, whereas genistin did not(25).
4. Etc.
E3. Diet to prevent Glomerulonephritis
1. Flaxseed
In the study to evaluate Flaxseed: a potential treatment for lupus nephritis, showed that 30 g flaxseed/day was well tolerated and conferred benefit in terms of renal function as well as inflammatory and atherogenic mechanisms important in the pathogenesis of lupus nephritis(26).
2. Green tea
In the study to investigate whether the anti-inflammatory and antioxidant properties of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) favorably affect the development of immune-mediated GN, researchers at the Shanghai Tenth People's Hospital of Tongji University, found that levels of glutathione peroxidase and peroxisome proliferator-activated receptor-γ (PPARγ), both reduced in the vehicle-pretreated diseased mice, were normalized. This renoprotective effect was reversed by concomitant administration of the PPARγ antagonist GW9662 throughout the EGCG pretreatment period. Importantly, mortality and renal dysfunction were significantly attenuated even when the polyphenol treatment was initiated 1 week after the onset of GN. Thus, EGCG reversed the progression of immune-mediated GN in mice by targeting redox and inflammatory pathways(27).
3. Soy
According to the study of Beneficial effects of soy protein consumption for renal function by Anderson JW. at the University of Kentucky, substituting soy protein for animal protein usually decreases hyperfiltration in diabetic subjects and may reduce urine albumin excretion. Limited data are available on effects of soy peptides, isoflavones, and other soy components on renal function on renal function in diabetes(28).
4. Etc.
F. Treatment
F.1. In conventional medicine perspective
Treatment depends on the underlined causes, symptom and types of glomerulonephritis (Acute or chronic)
F.1.1. If the causes of the disease is the result of hypertension
Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. High blood pressure means raising pressure in your heart and staying high over time, damaging the body in many ways.
1. Diuretics
Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes(29), according to the study by Department of Internal Medicine, University of Pisa(29).
2. Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor agonists
In the study of a total of 25,035 hypertensive patients newly prescribed an ACE inhibitor or angiotensin II receptor blockers (ARBs), no differences were found in risk of death, coronary disease, chronic kidney disease, or stroke between those prescribed ACE inhibitors and those prescribed ARBs. Patients prescribed ARBs had a greater rate of new-onset diabetes (hazard ratio [HR], 1.28; confidence interval [CI], 1.08-1.52), and this was especially true for women (HR, 1.93; CI, 1.22-3.07). Within a large medical-practice based population, there was no evidence of differential effectiveness between ACE inhibitors and ARBs for most outcomes, with diabetes being the notable exception(30).
3. Etc.
A.2. If the causes of the disease is the result of infection due to invasion of bacteria
Corticosteroid therapy with antibiotics
There is a report of a 24-years old man who presented to the hospital with fever, fatigue, and rapidly progressive glomerulonephritis. Although renal function in the case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure, according to the study by Shiga University of Medical Science, Seta(31).
A.3. Lupus or vasculitis
Lupus is a chronic, autoimmune disease as as a result of the development of autoantibodies that attack the systems and organs in the body.researchers at the indicated that saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production. Immune-suppressing drugs can be prescribed to control inflammation.
Immune-suppressing drugs
Tacrolimus, an immune-suppressing drug, at low dosage and serum level to be potentially effective and safe for treatment in patients with LN resistant to sufficient CYC therapy. A tacrolimus dosage of 2-3 mg daily appears to be effective and safe, according to the study by Peking Union Medical College Hospital, Chinese Academy of Medical Sciences(32)
A.4. IgA nephropathy
Treatment strategies have included management of blood pressure and lipids, improvement or stabilization of kidney function, and reduction of proteinuria. Supportive therapies, including angiotensin blockade, should be considered as first-line therapy for patients with urine protein >0.5 g/day and/or blood pressure >140/90 mm Hg. Corticosteroids could be considered as add-on or monotherapy for patients with urine protein >1 g/day with preserved renal function, but conclusive data are lacking for general treatment recommendations for the use of other therapies for IgAN(33).
A.5. Etc.
B. In herbal medicine perspective
According to the research of Herbal treatments of glomerulonephritis and chronicrenal failure: Review and recommendations by Rainer Nowack, Felipe Flores-Suarez, Rainer Birck, Wilhelm Schmitt and Urs Benck(34), some herbs below may have certain effects in treating glomerulonephritis.
1. Astragalus
In the study to evaluate the effect of APS on glomerulonephritis rats induced by cationic Bovine Serum Albumin(C-BSA) by flow cytometry using Nuclear Transcription Factor-kappaB (NF-kappaB) as marker, showed that the expression of NF-kappaB and the concentration of IL-2, IL-6 and TNF-alpha were significantly decreased in the treatment group. This study clearly suggests that APS is effective in protecting against glomerulonephritis induced by C-BSA through the inhibition of NF-kappaB mediated-cytokine pathway(35).
2. Rhubarb
In the study of the evidence of the effect of Rhubarb in immune complex GN induced in rats by injection of anti-thymocyte serum (ATS), researchers at the Department of Nephrology, Drum Tower Hospital, indicated that Rhubarb-treated anti-Thy-1 animal model should develop significantly less matrix expansion. Rhubarb also inhibited synthesis and secretion of fibronectin, an important component of mesangial extracellular matrix. Decreased IL-1 activity might be involved in the therapeutic effect of Rhubarb on mesangioproliferative glomerulonephritis(36).
3. Perilla frutescens
In the study to evaluate the anti-nephritic effects of perilla in HIGA mice that spontaneously develop high levels of serum immunoglobulin A (IgA) along with mesangial IgA deposition, researchers at the Graduate School of Pharmaceutical Sciences, Kyoto University, showed that Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in HIGA mice. Cultured Peyer's patch cells and spleen cells from perilla-treated mice produced significantly less IgA than controls. Rosmarinic acid, by itself, suppressed serum IgA levels and glomerular IgA deposition in HIGA mice. Cultured spleen cells from RsA-treated mice produced less IgA than controls(37).
4. Dan Shen and Sheng Mai Ye
In the study to investigate the effects of danshen(Salvia plectranthoides Griff.) and shengmaiye (Panax ginseng C. A. Mey, Ophiopogon japonicus Ker-Gawl and Schisandra chinensis Baill) on glomerulosclerosis induced by adriamycin in SD rats, showed that Dansheng and shengmaiye may play an important role in the treatment of glomerulosclerosis in rats(38).
5. Arctium lappa
In the study of the ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats, researchers at the School of Pharmacy, Second Military Medical University, found that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required(39).
6. Etc.
C. In Traditional Chinese medicine perspective
C.1. HTCM herbal formula: Huang Dan decoction (HDD) and Tripterygium Wilfordii (TW)
In the study to investigate the therapeutic effects of huangdan decoction (HDD) and Tripterygium Wilfordii (TW) compound tablet on membranous glomerulonephritis in rats, researchers at the Tongji Medical University, indicated that HDD and TW may alleviate the pathological lesions of MGN, prevent or retard its progression, and have remarkable therapeutic effects on MGN(40).
C.2. Shen Yan Yi Qi Ye
In the study using cationic bovine serum albumin (C-BSA) for duplicating experimental animal model of membranous glomerulonephritis with chronic renal failure, found that in the therapeutic group, the urine protein and serum creatinine were reduced as compared with those in pathological group, P < 0.01. The parameter of morphometric analysis of glomeruli such as mean diameter, mean perimeter, mean surface area, mean volume, mean cross sectional area were all decreased, P < 0.01, the number of glomerular proliferative cells and thickness of glomerular capillary wall were all attenuated, P < 0.01, as compared with those in the pathological group. It suggested that SYYQY might alleviate the glomeruli lesions and benefit the renal functions, according to the study by Beijing University of TCM(41).
C.3. Etc,
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