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Lupus Nephritis

SLE with Membranous Glomerulonephritis

Lupus nephritis is a complication that is most evidently associated with a condition called systemic lupus erythematosus (SLE). Once SLE has been diagnosed, significant precautions are done to ensure that any type of renal affectation is detected and treated early on to prevent worsening of the condition. However, lupus nephritis may be diagnosed even in the early stage of SLE, where patients may not show any symptoms of renal dysfunction yet.


Presentation

Patients who suffer from active stage lupus nephritis often have symptoms associated with active stage systemic lupus erythematosus (SLE). These are manifested by fever and fatigue, rash formation, and in complicated cases, manifests as arthritis, serositis, and other forms of morbidity invoving the central nervous system (CNS). These manifestations can be found in either focal or diffuse types of proliferative LN.

In rare cases, some patients show asymptomatic lupus nephritis, in which the condition can only be suggested after a series of regular consultations and laboratory examinations that reveal elevation in blood serum creatinine levels, lowered albumin concentration, urinary protein or sedimentation in blood. Asymptomatic LN is more typical in mesangial or membranous types.

Because of the high probability of renal affectation in active nephritis, the patients more commonly show peripheral edema as an effect of hypertension or inefficient reabsorption of albumin into the blood (hypoalbuminemia), attracting more fluid accumulation in the interstitial spaces instead. Overall edema or ascites is more common in diffuse or membranous types of LN, as the damage done on renal tissues often lead to massive proteinuria. From the hypertension commonly effected in diffuse types of LN, patients tend to experience headache and dizziness from the inefficient blood flow to cerebral tissues. Significant elevation of blood pressure may also cause patients to have visual disturbances, along with other symptoms that result from the cardiac circulation's effort to compensate.

Physical examination

For focal and diffuse types of lupus nephritis, the physical assessment may reveal manifestations that are generally seen in active SLE, showing presence of rash, ulceration of the oral and nasal mucosa, that in some cases worsen into synovitis and serositis. All in all, active LN patients show symptoms of hypertension, peripheral or generalized edema. The occasional effort to correct this imbalance often leads to cardiac decompensation. In membranous types of LN, signs of isolated nephrotic syndrome may be familiar. Patients with this complication can be observed with peripheral edema or ascites, pleural and pericardial effusions that manifest even in the absence of hypertension.

Fever
  • Both dengue fever and SLE have common manifestations of fever, arthralgia, rash, leucopenia with thrombocytopenia and serositis.[ncbi.nlm.nih.gov]
  • A 25-year-old woman presented with fever, arthralgia and proteinuria exhibiting leukopenia, hypocomplementemia, increased serum IgG and IgG4, and positive antinuclear and anti-double-stranded DNA antibodies.[ncbi.nlm.nih.gov]
  • CASE: A 29-year-old nullipara presented at 17 weeks with fever, vomiting, and costovertebral angle tenderness 1 week after being treated for a presumed urinary tract infection. On presentation, new-onset hypertension was noted.[ncbi.nlm.nih.gov]
  • An attack may produce no symptoms, but more often there are headaches, a rundown feeling, back pain, and perhaps slight fever. The urine may look smoky, bloody, or wine-colored.[medical-dictionary.thefreedictionary.com]
  • Recognize the signs of potential drug adverse events such as fever, chills, sore throat, cough, shortness of breath, blood in urine and diarrhea. Notify your doctors.[hss.edu]
Weight Gain
  • Lupus Nephritis Symptoms Symptoms of lupus nephritis may include: Swelling of the extremities, face Weight gain Hypertension Dark or foamy urine More frequent urination Blood in the urine Urinary tract infections Lupus Nephritis Diagnosis Penn's Lupus[pennmedicine.org]
  • They may include: Weight gain High blood pressure Dark urine Foamy, frothy urine The need to urinate during the night Not all urinary or kidney problems in people with lupus are due to lupus nephritis.[webmd.com]
  • Some of them can include: Hematuria: Blood in the urine Proteinuria: Protein in the urine—one sign of proteinuria is foamy urine Weight gain High blood pressure Edema: Extra fluids that cause swelling in areas like the legs and ankles Risk Factors There[reverehealth.com]
  • Lupus nephritis may cause weight gain, high blood pressure, dark urine, or swelling around the eyes, legs, ankles, or fingers. However, some people with SLE have no overt symptoms of kidney disease, which must be diagnosed by blood and urine tests.[kidneyurology.org]
Malaise
  • A 78 year old white male on methimazole due to Grave's thyroiditis presented with acute renal failure after a short term history of progressive shortness of breath, malaise, myalgias, arthralgias, and bilateral lower limb swelling.[ncbi.nlm.nih.gov]
  • A 20-year-old woman presented with malaise and edema in the lower extremities and face. She had multiple lymphadenopathies. There were 20% eosinophil in blood smear and 32% in bone marrow aspiration.[ncbi.nlm.nih.gov]
  • There may be slight malaise, but often the only indication of the disease is the presence of albumin and other abnormal substances in the urine. If a blood count is made during this stage, anemia may be found.[medical-dictionary.thefreedictionary.com]
  • Manifestation Prevalence, % Systemic: Fatigue, malaise, fever, anorexia, weight loss 95 Musculoskeletal 95 Arthralgias/myalgias 95 Nonerosive polyarthritis 60 Hand deformities 10 Myopathy/myositis 25/5 Ischemic necrosis of bone 15 7.[de.slideshare.net]
Rapidly Progressive Glomerulonephritis
  • Kidney problems associated with lupus nephritis range from asymptomatic protein in the urine to rapidly progressive glomerulonephritis, leading to end-stage renal disease.[clinicaltrials.gov]
  • The presentation of lupus nephritis is highly variable, ranging from mild asymptomatic proteinuria to rapidly progressive glomerulonephritis with haematuria and red cell casts.[ndt.oxfordjournals.org]
Hematochezia
  • Severe hematochezia continued despite ganciclovir administration, and the patient underwent laparoscopic total colectomy and partial ileostomy.[ncbi.nlm.nih.gov]
Left Flank Pain
  • A month later, the patient presented with left flank pain and weakness. A CT scan of the abdomen and pelvis showed a perinephric hematoma and the renal arteriogram revealed numerous microaneurysms within the kidney consistent with renal PAN.[ncbi.nlm.nih.gov]
Upper Abdominal Pain
  • Two months after admission when she was taking 40 mg of PSL and 1500 mg of MMF daily, she suddenly developed upper abdominal pain and multiple skin blisters, and disseminated visceral VZV infection was diagnosed.[ncbi.nlm.nih.gov]
Intestinal Perforation
  • The patient developed an intestinal perforation, and laparoscopic Hartmann's surgery was performed on the sigmoid colon.[ncbi.nlm.nih.gov]
Hypertension
  • PRES in systemic lupus erythematosis (SLE) is a rare clinical phenomenon and, when reported, it is associated with hypertensive encephalopathy. Our patient did not have hypertensive crisis, but had uremic encephalopathy.[ncbi.nlm.nih.gov]
  • Components of scoring system for proliferative LN consist of hypertension, eGFR[ncbi.nlm.nih.gov]
  • Microscopic haematuria and hypertension may also been seen.[en.wikipedia.org]
  • Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one case and in a small for gestation age in both cases.[ncbi.nlm.nih.gov]
  • hypertension (eg, BP 130/80 mm Hg) or proteinuria.[msdmanuals.com]
Ulcer
  • She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema.[ncbi.nlm.nih.gov]
  • In clinical data, photosensitivity and mouth ulcers were more common in the female patients, while males had more serositis and vasculitis.[ncbi.nlm.nih.gov]
  • Manifestation Prevalence, % Cutaneous 80 Photosensitivity 70 Malar rash 50 Oral ulcers 40 Alopecia 40 Discoid rash 20 Vasculitis rash 20 Other (e.g., urticaria, subacute cutaneous lupus) 15 Hematologic 85 Anemia (chronic disease) 70 Leukopenia ( 8.[de.slideshare.net]

Workup

The diagnostic procedure usually done for patients suspected with SLE is urine analysis with emphasis on determining serum creatinine levels. This immediately gives the impression of the renal affectation normally found early in the disease process. For the diagnosis of LN, renal biopsy is suggested to all patients with SLE, especially for those that have initial urinalysis tests showing proteinuria with microscopic fragments of blood components (hematuria), and erythrocytes (RBC) in the urine. These abnormalities in excretory systems if coupled with hypertension, encourages the practitioner to suspect for renal involvement. Renal biopsy is suggested also even in some cases with irrelevant hypertension, most especially when presence of elevated serum creatinine levels, irregularities in urine examination and symptoms of undiagnosed SLE appear in concert.

Initially, the urine composition and blood serum creatinine level is measured after assessing patients. If either of the two shows abnormal results, renal biopsy is automatically done to confirm LN. Examination of, the classification of LN is identified to determine the severity of organ involvement during the time of diagnosis. This system of histologic subtyping of lupus nephritis greatly contributes to determine prognosis from the disease, as influenced by the severity of systemic affectation, and also helps to modify the treatment approach.

Some subtypes of LN may manifest symptoms same to that in glomerular diseases, the main reason being that both conditions damage the tissues of the kidney. One example is that the membranous and diffuse proliferative type lupus LN can be compared to idiopathic membranous glomerulonephritis. Type I LN on the other hand, is found to be similar to the manifestations of membranoproliferative glomerulonephritis. Overlapping in between the categories is commonly observed, and more patients show a progression from one subtype and onto another throughout the disease process.

  • Class II: Mesangial proliferative lupus nephritis
  • Class III: Focal proliferative lupus nephritis 
  • Class IV: Diffuse proliferative lupus nephritis 
  • Class V: Membranous lupus nephritis 

Patients with LN are regularly monitored for signs of renal dysfunction and are closely watched for any complications that could arise from SLE. Moreover, an increase in blood serum creatinine level indicates renal dysfunction, while a decrease in serum component levels or a significant measure in anti-DNA bodies in blood titer would reveal that there is increased white blood cell (WBC) activity that suggests proliferation of autoimmune complexes [7].

Bilateral Small Kidneys
  • Relative contraindications to biopsy include the presence of a bleeding diathesis, solitary kidney and advanced kidney disease with bilaterally small kidneys.[ndt.oxfordjournals.org]
Small Kidney
  • Relative contraindications to biopsy include the presence of a bleeding diathesis, solitary kidney and advanced kidney disease with bilaterally small kidneys.[ndt.oxfordjournals.org]
Foam Cell
  • Kidney biopsy showed diffuse global lupus nephritis (World Health Organization class 4-G A/C) with many intraglomerular foam cells containing cholesterol crystals.[ncbi.nlm.nih.gov]

Treatment

The ultimate objective of therapy in LN is to correct the renal filtration mechanism or perhaps the very least, prevent further renal deterioration of whatever remains functional. Medical management and therapy modes can vary according to the degree and pathological damage done to the renal tissue, therefore explaining the need to identify the LN subtype beforehand. It is also important to treat non-renal illnesses that contribute to kidney malfunction, especially taking into consideration how to maintain the buffer mechanisms that naturally resolve inadequate glomerular filtration rates [8] [9] [10].

Corticosteroid therapy are basically the chosen pharmacological approach to combat severe stages of renal failure. However, for certain types of LN characterized by proliferative lesions in the renal tissue, the efficacy of immunosuppressant drugs have enhanced outcomes. The drugs of choice for immunosuppressive therapy are azathioprine, cyclophosphamide, and mycophenolate mofetil, any of which can conveniently be administered to patients hypersensitive or may show poor response to corticosteroid therapy.
If hypertension is manifested, it should be promptly resolved. Doing this has enabled higher chances of renal recovery. Proteinuria, being a common symptom of kidney malfunction and other nephropathies, is treated by routine administration of angiotensin II receptor blockers (ARBs), and angiotensin-converting enzyme inhibitors (ACEIs).

Diet management is essential to all patients with LN, especially for common cases with hypertension where protein and fat intake may already be restricted early in treatment, even though protenuria or albuminuria has not been manifested yet. Clearly, diet is even more strictly monitored for patients with renal insufficiency, but there is great benefit to using lipid-lowering medications called statins, in combating hyperlipidemia. For nephrotic syndrome-influenced hyperlipidemia, failure to manage diet restrictions may significantly worsen the impaired renal functions.

Calcium supplements play a big role in preventing osteoporosis that may result from long-term intake of corticosteroids, in addition, some practitioners encourage intake of bisphosphonate supplements as complement to calcium once improved renal function has been achieved. Nephrotoxic agents such as non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated medications to LN patients tested with little to significant elevation in blood creatinine levels, and are taken with great caution and only after confirming laboratory tests. Opting for the classic non-acetylated salicylates on the other hand, provides a much safer treatment regimen to counteract symptoms of inflammation, even when renal involvement is present.

One highly noted contraindication to LN in active stage is pregnancy, for the many reasons and ways that it could worsen the mother’s systemic condition. One reason is that pregnancy requires an even more pronounced workload on the kidneys that could further contribute to renal failure, if the body fails to compensate, and second is that most of the treatments given for LN patients are extremely teratogenic.

And finally, patients that have complicated into end-stage renal disease (ESRD), multiple sclerosis, or have reached a high index of chronicity in the illness process would most likely not respond to any form of aggressive approach in treating LN. For cases like these, therapy will be more geared towards manipulating and correcting a number of non-renal abnormalities that could control the symptoms of SLE and if possible, aid in the successful transplantation of new kidney organ/s.

Guidelines

In 1999, the ACR released a set of guidelines in the aim of providing useful information for practicing physicians and healthcare professionals in handling patients with SLE. This guide included essential recommendations for the management of complications such as lupus nephritis. The key recommendations for LN are the following:

  • Patients with clinical manifestations of active, and untreated lupus nephritis are advised have a renal biopsy performed initially to classify and identify the disease according to the criteria of the International Society of Nephrology and/or the Renal Pathology Society.
  • All clients diagnosed with lupus nephritis best undergo basic hydroxychloroquine therapy, unless strongly contraindicated with any other complications. This recommendation is deduced from a controlled study that showed prospective results of producing lower numbers of flare episodes among patients who continued with hydroxychloroquine therapy, compared to those who discontinued and were given placebo instead.
  • Glucocorticoid therapy, done in synergy with cyclophosphamide which is administered intravenously, or in combination with mycophenolate mofetil, administered orally, are two methodologies recommended during the induction phase for patients classified with ISN - III/IV disease.
  • Patients classified with ISN/RPS - I and II nephritis may or may not undergo immunosuppressive drugs as this is not required.
  • High levels of proteinuria, measuring 0.5 g or more in 24 hours, should be managed by administering ACE inhibitors or drugs classified as angiotensin-receptor blockers.
  • The patient's blood pressure should be maintained at 130/80 mm Hg or lower.

Prognosis

In the general medical scene, there has been continuous modernization in the treatment approach and therapeutic care for lupus nephritis, and this led to improvements in kidney ailment recovery and in the overall survival of patients from the disease. In the 1950s, the chances of reaching up to 5 years for patients with LN was very unlikely, almost to the rate of 0%. Now as a result of the discovery of the synergistic effect of administering immunosuppressants, the statistics have changed. The induction of immunosuppressive drugs such as pulse cyclophosphamide via intravenous route, improved survival rates of reaching up to 5 years up to 85%, while survival to 10 years went up to the rate of 73%. Other illnesses that are commonly found to be associated with LN are those that are derived from the disruption of normal kidney function, nephrotoxicity and other adverse effects from the medications.

Progressive and chronic renal involvement later produces imbalances in the blood such as anemia, uremia, shifts in pH of plasma, and abnormalities in electrolyte concentration. Glomerolunephritis and other nephrotic-related symptoms would be edema, overall ascites and increased lipid levels in blood, therefore increasing predisposition to thrombosis and then later on to coronary artery disease (CAD) and cerebrovascular attacks (CVA). Hypertension from ascites and renal dysfunction even greatly increases the risk of CAD and in severe cases could lead to CVA. A particular study done found that LN in younger ages or early onset are in greater risk of developing ischemic heart disease.

Some of the comorbities from the drug therapy may worsen into cardiovascular disease and thrombolytic complications as different drug actions are taken into consideration. Combined treatment with corticosteroids, cyclophosphamide, and immunosuppresants for the treatment of LN increases the risk of superinfection. Meanwhile, the single approach of corticosteroid therapy itself, when done on long term, is known to predispose patients to hypertension and diabetes mellitus, which in combined effect may lead to avascular necrosis. Osteoporosis is one late-onset complication known to result from long-term corticosteroid therapy. On the other hand, cyclophosphamide therapy in itself predisposes patients to blood disorders such as cytopenias, hemorrhagic cystitis, and high risks of malignancy. Infertility is one adverse effect from cyclophosphamide therapy.

Etiology

SLE is an autoimmune disease that can affect multiple systems of the body at one time. The nature of its pathogen and etiologic process are still idiopathic. Autoimmunity in SLE is related to an intolerance with one’s own antibody mechanism that may have resulted from an insufficient silencing of the autoreactive lymphatic system, therefore presenting both central and peripheral affectations at the same time. In this condition, there is continuous and uncontrolled apoptysis of cells by the hyperactive lymphocytes that results to the proliferation of dead cell membranes that is then weakly filtered out of the circulation. The autoimmunity could then be contributed by the disruption of the normal response due to overexposure of lymphocytes to apoptotic cellular and nuclear fragments that are continuously present in its lymph vessels.

The creation of immune complexes from self-antigens binding with DNA, phospholipids and other blood components and being distributed back into the circulation supports two the mechanisms involved. Although the causes of SLE is generally unknown, there are existing contributing factors such as being predisposed genetically, severe viral infections that may have disrupted normal immunoregulatory mechanisms, as well as other environmental phenomena that may have triggered unexplained autoimmune alteration in certain groups or populations.

More recent studies conclude that a specific genetic involvement can also be linked to the chances of developing renal disorders among patients with SLE. This is highly probable among certain groups with ethical backgrounds, such is European-American ethnicity and that of African-American groups. The studies that were conducted also determined how certain groups were found to influence the ireversibility of the glomerular affectation when complications in the kidney occur [4] [5].

Epidemiology

United States statistics

SLE, being a rare disease has the prevalence ratio of 1:2,000 in the general statistics. However, researchers suspect there could be an underestimation due to factors like difficulty in diagnosis and unrecorded SLE cases and claim that the ratio may be somewhere in between 1:500 or 1:1000 in general. Pathologically, the kidneys are the organs with higher degree of affectation in patients suffering from SLE. Renal complications were estimated to range from 30%-90% in other published surveys, while the true chances of Lupus nephritis occurring in relation to SLE is as high as 50%. This percentage for LN is significantly increased for groups with ethnic background and children, taking genetic predisposition into consideration.

International statistics

A review of epidemiologic records on the occurrence of SLE in the Canada, United States, Europe, Asia, and Australia, have shown that disparities in the numbers were present. It showed that there is a higher probability for non-white populations in Canada, United States, Europe, and Australia to acquire the disease.
Worldwide, a higher trend for the disease can be found in Europe and Australia than in the US. Much lower incidence of SLE was reported in the country of Japan. Among European countries, there was significantly higher prevalence in Sweden, Iceland, and in Spain. These differences may however indicate a great variability on the actual occurrence of SLE across the studied populations or may be directly influenced by different survey methodologies.
As early as in diagnosis, patients with SLE were already found to develop lupus nephritis, and more cases of renal affectation were diagnosed during the preliminary stages of SLE. More common in women, SLE manifests for females in their 30s, but generally the disease process can be seen in patients aged 20 to 40. For uncommon cases, children with SLE tend to be more at risk for developing LN and sustain more complications secondary to severity of disease development and high toxicity in medical management.

Sex-related demographics

As was mentioned, the occurrence of SLE is more probable in women with a female-male ratio of 9:1, in which study women were also more likely to develop LN than male patients. However, the severity of renal disease derived from SLE can be worse in nature for males while women tend to have a high prognosis rate.

Race-related demographics

SLE was found to be more prevalent in Hispanic populations and African-American groups than in white people, and cases of severe lupus nephritis were higher among the Asians and among African Americans compared to other groups with ethnic backgrounds.

Sex distribution
Age distribution

Pathophysiology

The cause of SLE may still be unknown, but its pathophysiology can be deduced from the tissue affectation commonly manifested in patients. A special pattern of tissue injury creates the impression that different effector reactions may have acted singularly or in mutilple ways to show the classic pleomorphic patterns of LN. When Fc receptor-mediated inflammation or a cytotoxic reaction has taken place, autoantibody reactions may lead to cell injury and tissue scarring as a complementary effect, as can be seen in cases with antibody-mediated and hemolytic types of anemia or thrombocytopenia.

Autoantibody binding in the kidney often occurs with intrinsic renal antigens, such as the cellular components and glycoproteins found in cell surfaces. Renal damage in lupus nephritis is the outcome of structural binding between autoantibodies in the system and the circulating blood antigens, which later form into circulating immune complexes. Some autoantibodies bind to antigens that are present in the glomerular and vessel walls, forming what is called in situ immune complexes. The same cellular activity can be seen for nucleosomes in the circulation and for antidouble-stranded DNA autoantibodies.

Following this, the Fc receptor and formation of complexes prompts an inflammatory response similar to a cytotoxic reaction. This cytotoxic reaction could be directly correlated with podocytes in influencing the development of nephropathy in membranes where in situ immune complexes were formed. These are usually attached along the inner epithelial layer of the glomerular base membrane, and sometimes around the endocapillary cells in cases where there is significant proliferation and exudate formation.

More than the direct cell and tissue injury that could result from the formation of these immune complexes, another complications from LN is thrombosis and vascular damage that could result from the binding of autoantibodies with antiphospholipid components or with cryoglobulins. In understanding lupus nephritis, a subgroup of patients was surveyed to find out about the nature of antineutrophil cytoplasmic-antigen autoantibodies (ANCA), which as a result was found to develop into vasculitis, and even glomerulonephritis by way of a "pauci-immune" mechanism that is particularly dependent on neutrophil activity. This mechanism is similarly observed in rare conditions namely, microscopic polyangiitis, and Wegener's granulomatosis.

To conclude with emphasis on the idiopathic nature of the etiology of LN, it is still commonly assumed that some unfamiliar groups of antibodies with no known specificity nor classification, may contribute to the pathogenesis of other subtypes of LN, say for example, the components that function as anti-endothelial antibodies [6].

Prevention

As with all types of illnesses, preventing all possible complications is always key to good prognosis. Having known that lupus nephritis is a very common complication in SLE patients, acknowledging its immunologic nature will aid the healthcare professional in implementing appropriate prophylactic management.

LN is a result of inflammation from the proliferation and deposition of immune complexes in the kidney. Normally, immune complexes are excreted through discharges in healthy individuals, but for immunodeficient patients with SLE, these immune complexes get into the blood circulation and is then observed to cause autoimmune effects on random parts of the body. Because of this abnormal composition of the blood, the kidney being in charge of filtering all foreign and harmful components in blood will begin to dysfunction depending on the damage done in the renal tissue. Therefore, the best approach is to be aggressive in preventing any form of kidney affectation most commonly found in SLE.

  1. Prevent contraction of infection and community-acquired colds: Any form of infection or colds encourage formation and further proliferation of immune complexes to the glomerular base membranes. Colds and infections should be aggressively treated being these are the most commonly acquired by immunosuppressed individuals, and assuming to prophylactic measures such as wearing masks, intensive hygiene or even isolation are essential. Performing these measures, coupled with the health practitioner's inherent skills in intensive care, can significantly lower the risk of LN in SLE patients. Other than this, promotion of healthy regular exercise can also improve in strengthening immunity against airborne infections.
  2. Avoid nephrotoxicity from medications: Most medicines are nephrotoxic in nature especially those that are synthetically derived and chemically modified. Pain relievers rarely result to kidney failure, especially when used only in short term and only as needed. However, if such drugs are taken daily for maintenance or if a drug-dependence has developed with continual use, the kidneys become weak from the constant effort to filter these strong elements. The practitioner can then opt for more non-intoxicating modes of therapy that can achieve both the desired therapeutic effects without harming renal integrity.
  3. Activities of daily living: Promoting tolerable activities of daily living, and aiming to improve performance each day can boost the patient's immune system against common infections. The patient can benefit greatly from good motivational support and access to available modalities for promoting wellness. Since LN is a subsequent event of compromised renal function, increasing the patient’s innate coping mechanisms to physiologic stress, and their ability to manipulate modifiable factors to avoid adding workload to the kidneys can be very beneficial in the long run, proving more effective when this is done in the early stages of SLE. Modifiable factors include cessation of smoking and other habits like drinking alcohol.

On the contrary, this manner of approach to preventing LN in patients can only reduce the risks but cannot absolutely guarantee non-prevalence of developing the complication throughout the course of SLE. This mode of prophylaxis may prove more effective for SLE that is diagnosed during its non-proliferative or earliest stages.

Summary

Lupus nephritis (LN) is a complication associated with systemic lupus erythematosus (SLE). From a study previously done in the US, it was found that about 35% of a group of adult patients diagnosed with systemic lupus erythematosus (SLE) exhibited early symptoms of lupus nephritis about the same time during the diagnostic procedure, while an approximate total of 50% to 60% of the patients under the same study revealed to have developed nephritis within 10 years time from the onset of SLE. In terms of gender, nephritis has been evidently more prevalent in males than in females. One factor that contributes to the prevalence of the disease could be genetic in nature, and can be correlated with race as it is more evident in Hispanics and African Americans as compared to Caucasians. However for patients that have developed the disease, renal affectation can be often observed in non-Caucasians. The prognosis of lupus nephritis while associated with SLE reaches up to 95% within 5 years from the time of diagnosis, and up to 92% within 10 years. However, at a rate of 88% in prognosis, survival rates decrease for chronic lupus nephritis that reach 10 years and above, with much even poorer prognosis for African American patients.

In order to improve therapeutic care for patients with SLE, the American College of Rheumatology (ACR) published a set of basic guidelines in 1999 to provide education for primary health care professionals and physicians. This compiled all new information that is concerned with the provision of ideal care for specific manifestations of SLE, as well as those of other possible complications that may arise from the condition. Included in this guide are the recommended methods of care for patients who developed or complicated into lupus nephritis, and pharmacologically, this consists of treatment using glucocorticoids, beginning in small doses and then followed by daily high doses of glucocorticoid in combination with immunosuppressants. In addition to this, the immunosuppressive action of cyclophosphamide has proven to be most effective in resolving diffuse proliferative glomerulonephritis for patients with renal affectation.

On the other hand, Mycophenolate mofetil has not been used yet for lupus nephritis, and no information about the drug was mentioned in the study. During that time, several clinical studies were done to determine the additive effects of using glucocorticoids in combination with immunosuppressive drugs, and as published, some trials proved to be prospective in terms of efficacy, while the remaining outcomes from the same study were randomized.

The ACR then came to conclude that a recommended approach to LN treatment was essential. After conducting a review of records and acquiring expert advice from highly qualified professionals such as rheumatologists, nephrologists and pathologists, a set of guidelines was then devised. The strategies formulated generally applies to adult patients with LN, particularly for recipients of care in the US, and were conveniently incorporated to match the available methodologies of care available in the country as of April 2011.

However meticulously done, the guidelines still have considerable limitations for performing individualized patient care, thereby naming and using the term "recommendations" instead of claiming them as standard methods of care. Therefore, not any part of the published guidelines should be used as an absolute resource material for making any major clinical decisions, nor should it be used in setting limits for providing care for patients with LN. Instead, it can only serve basically as a source of expert tips and clinical deductions from different healthcare professionals for practicing physician looking to get a second opinion [1] [2] [3].

Patient Information

Lupus nephritis (LN) is a kidney disorder and is commonly a complication that is found to develop in clients confirmed to have systemic lupus erythematosus (SLE).

Causes

SLE, or most commonly known as lupus, is an autoimmune abnormality that can destroy tissues in different areas of the body wherever the blood flow can dislodge immune complexes.  This can be further described as a disorder that causes one's own antibodies to act against its own lymphatic components.

The immunologic agents of the human body, in its effort to act as the front line body defense against infection and other foreign substances are the same components that ironically trigger ill-functioned immune responses in the host. Patients with autoimmune disorders in general have malfunctioning immune detectors that are unable to recognize and distinguish between the abnormal flora from that of the natural healthy flora. This results to the unfortunate destruction of healthy cellular components and tissues of the body.

SLE carried by blood all throughout the body of an individual more commonly creates lesions in the kidney tissues, in its membranes and cause other renal affectations all because the kidneys tend to filter blood more profusely as a defense mechanism. This therefore leads to symptoms of interstitial type of nephritis, or nephrotic syndrome and in some cases, infection in the glomerular basement membrane where filtration of blood mainly occurs, more commonly known as glomerulonephritis (GN). When renal manifestations start to develop into disorders such as LN, the SLE may rapidly complicate into kidney failure.

LN is statistically known to affect with an approximate ratio of 3:10,000 people. For children that have developed SLE, about 50% of them would likely develop some subtype or degree of renal involvement. Surprisingly though, more than 50% of patients have not shown symptoms of SLE at the time they were diagnosed with LN. SLE is more commonly diagnosed in females and more likely develops at 20 - 40 years of age.

Symptoms

Physical assessments that reveal lupus nephritis include:

Presence of blood fragmentations in the urine
Foamy consistency of urine
Significant increase in blood pressure
Swelling or fluid accumulation in any part of the body

Laboratory examinations and tests

Initial examination may show visible signs of compromised renal functioning such as fluid accumulation or swelling (edema). When edema is coupled with constantly increased blood pressure, this highly suggests the presence of renal insufficiency. Abnormal heart and lung sounds may also be hears by the physician upon auscultation.

Diagnostic procedures for early detection of LN include:

  • Blood serum ANA titer
  • Blood-Urea-Nitrogen (BUN) and creatinine levels
  • Complement blood levels
  • Analysis of urine charachteristics and composition
  • Urine protein (proteinuria/albuminuria)

However, not all of these show up positive in all cases of SLE and still needs to be confirmed further using other diagnostic techniques. A renal biopsy cannot absolutely diagnose lupus nephritis, in SLE patients, but it aids in determining the best mode of treatment according to the level of renal damage discovered.

Treatment

The main objective of therapy for LN is to correct kidney impairment and cautiously delay end-stage renal failure. Drugs of choice include therapy with steroids or corticosteroids and other medications helpful in suppressing the immunologic hyperactivity, such as azathioprine, therapy with cyclophosphamide, or with mycophenolate mofetil.

Some patients may find the need to undergo dialysis to be relieved from uncontrollable symptoms of renal dysfunction, even for a short while. Kidney transplant is most recommended, however, patients with lupus in the active stage are discouraged to have transplantation because this would make it more probable for LN to occur in the new kidney organ/s as well.

Prognosis

A patient's chances of surviving is dependent on the particular subtype of lupus nephritis. Patients are warned about experiencing flare-ups, followed by asymtomatic episodes, and vice versa. Complicated cases of LN develop into chronic kidney failure, and if uncontrolled, may eventually lead to end-stage renal disease. It has been stated that LN could more likely recur in transplanted kidney/s, but this approach shows more prospective in prognosis as it seldom leads to end-stage renal disease. Other possible complications:

References

Article

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  2. Tunnicliffe DJ, Singh-Grewal D, Kim S, Craig JC, Tong A Diagnosis, monitoring and treatment of systemic lupus erythematosus: A systematic review of clinical practice guidelines. Arthritis Care Res (Hoboken). 2015 Mar 16. doi: 10.1002/acr.22591
  3. Wilhelmus S, Alpers CE, Cook HT, Ferrario F, Fogo AB, Haas M, Joh K, Noël LH, Seshan SV, Bruijn JA, Bajema IM. The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions. J Am Soc Nephrol. 2015 Jul 7.
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Last updated: 2019-07-11 21:53