Patients with lupus nephritis already have varying clinical manifestations of SLE. These clinical symptoms include malar or discoid rash, photosensitivity, serositis, oral ulcers, nonerosive arthritis, seizures, psychosis, or hematologic disorders. Lupus nephritis is diagnosed through laboratory findings, such as proteinuria or cellular casts. Typically, patients with LN are asymptomatic. Some patients with lupus nephritis may develop polyuria, nocturia, foamy urine, hypertension, and edema. Early signs of proteinuria, which indicate tubular or glomerular dysfunction, are the presence of foamy urine or nocturia. If the degree of proteinuria meets the nephrotic syndrome criteria of more than 3.5 grams per day of protein excretion, then peripheral edema develops due to hypoalbuminemia. There may also be microscopic hematuria that is not grossly visible.

Laboratory

With active SLE, complement levels (C3 and C4) are usually low with the presence of anti-dsDNA autoantibody. Creatinine (Cr) may be elevated or normal with the presence of proteinuria. Urinalysis shows the presence of proteinuria, microscopic hematuria, red blood cells, or red blood cell casts. The presence of protein in urine indicates glomerular damage. Proteinuria that exceeds more than 3.5 g per day is in the nephrotic range. If significant proteinuria exists, complete metabolic panel (CMP) will show low albumin count. 

Screening for proteinuria and hematuria is recommended every three months in active SLE.

Radiographic 

Bilateral kidney ultrasound should be obtained to rule out hydronephrosis or obstructive cause.

Biopsy

A kidney biopsy is indicated when the patient develops nephrotic range proteinuria.

Treatment is largely based on the class types of lupus nephritis as discussed in the histopathology section. Class I and II may generally be monitored and do not need treatment. Immunosuppressive and steroid treatment is needed with class III and IV. Renal replacement therapy is considered in class VI where most of the glomeruli have sclerosed. Active disease in LN typically predicts a better response to treatment, unlike chronic disease.

Treating risk factors that may cause progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) is also important. Starting a statin medication to lower lipids is necessary since CKD increases cardiovascular morbidity and mortality. Antihypertensive therapy with either angiotensin-converting enzymes (ACE) inhibitors and angiotensin II receptors blockers (ARBs) in patients with proteinuria and/or hypertension is indicated.

Treatment of lupus nephritis includes the induction phase and the maintenance phase using immunosuppressive and nonimmunosuppressive therapies. The induction phase is primarily used to elicit a renal response through the use of immunosuppressive agents and anti-inflammatory medications. After obtaining a renal response, maintenance therapy is used for a prolonged period with immunosuppressives and nonimmunosuppressives. This prevents relapse but requires regular monitoring while on the therapy. During induction therapy, prophylaxis against pneumocystis pneumonia. A concern with chronic glucocorticoid use is a loss of bone density. Taking appropriate measures to prevent bone density loss with appropriate supplementation and a baseline DEXA scan is important.[8][9]

Class III and IV Induction Therapy

Mycophenolate mofetil for 6 months with 3 days of intravenous glucocorticoid followed by prednisone tapered to the lowest dose. After 6 months, if there is an improvement, continue on a lower dose of mycophenolate mofetil or azathioprine. If there is no improvement or sufficient renal response after 6 months, switch to cyclophosphamide with pulse glucocorticoid followed by daily glucocorticoid. If there is a good renal response to this, the patient may be maintained on a low dose mycophenolate mofetil or azathioprine. If there is no response to the cyclophosphamide-glucocorticoid treatment, the patient may be trialed on rituximab or calcineurin inhibitors with the addition of glucocorticoid. This induction therapy is used more for Hispanic and African American race.

An alternative to mycophenolate mofetil is starting induction therapy with cyclophosphamide and pulse dosing of glucocorticoid for 3 days followed by oral prednisone taper. If the patient has European ancestry, then therapy would be transitioned into low-dose cyclophosphamide followed by oral mycophenolate mofetil or azathioprine. If the patient does not have European ancestry or white race, then treatment after prednisone taper would be transitioned to high dose cyclophosphamide for six months. After 6 months of therapy with either low or high dose cyclophosphamide, the renal response is assessed. If there is a good renal response, then the patient may transition to maintenance therapy with mycophenolate mofetil or azathioprine. If there is poor or no renal response, the patient would continue high-dose mycophenolate mofetil with pulse glucocorticoid followed by oral prednisone for another 6 months. Afterward, if there is no improvement, the patient should be trialed on rituximab or calcineurin inhibitor with glucocorticoid therapy. If there is a good renal response, the patient may be transitioned to maintenance therapy of low dose mycophenolate mofetil or azathioprine.

Class V Induction Therapy

Mycophenolate mofetil high dose with prednisone is started for 6 months. If there is a good clinical response, then maintenance therapy is resumed with either mycophenolate mofetil at a lower dose or azathioprine. If no improvement, then cyclophosphamide with pulse dose glucocorticoids is continued for an additional 6 months.

Treatment of Class III, IV, and V in pregnancy differs from the typical treatment previously discussed. Glucocorticoids are used in active lupus nephritis, either prednisone, dexamethasone or betamethasone. Azathioprine may be included if doses of glucocorticoid may be reduced. If a pregnant female patient has mild lupus nephritis, hydroxychloroquine is used as primary treatment. If instead, the pregnant female has clinically active lupus nephritis, then prednisone specifically is started.

Differential diagnosis includes other causes of nephrotic syndrome, nephrolithiasis, hydronephrosis, acute kidney injury due to medication, and acute interstitial nephritis.

Although lupus nephritis does have associated morbidity and mortality, the prognosis of LN relies on which WHO histopathology class it specifically meets. Class I (minimal) and Class II (proliferative mesangial) share a good long-term prognosis. As lupus nephritis progresses and advances different classes, then prognosis worsens. Class III has a poor prognosis. Class IV has the poorest prognosis. Prognosis also depends on how early therapy is initiated. The earlier the therapy is started in the disease course then, the better the disease outlook in lupus nephritis.

The management of lupus nephritis is an interprofessional that includes a nephrologist, hematologist, rheumatologist, internist, cardiologist, and an intensivist. The aim of treatment is to prevent progression of renal disease. These patients need very close monitoring because not only does lupus have high morbidity, but the drugs used to manage the symptoms also have a number of serious adverse effects. The overall prognosis for patients with lupus nephritis is guarded. When the disease advances, end-stage renal failure is inevitable.[5][10] (Level II) Patients should be educated about renal transplant and its benefits before the disease has progressed.