Case 1: 35-year-old patient with lupus nephritis presents with anasarca, hypertension and renal insufficiency at her 18th week of pregnancy

Liz Lightstone, and Sandra Navarra

Clinical presentation A 35-year-old female was diagnosed lupus nephritis (LN) 7 years earlier with kidney biopsy showing LN Class IV-G activity 7, chronicity 3. She received methylprednisolone pulse and was thereafter maintained on prednisone, hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) and calcium plus vitamin D. Her condition was ‘stable’ despite erratic follow-up and poor adherence. Two months ago, while on prednisone 10 mg/day, she consulted at clinic because of anasarca and hypertension at Week 18 of her 4th pregnancy. Obstetric history included two spontaneous abortions at 2 months gestation in 2013, 2015 and a successful term pregnancy in 2018 with a healthy baby girl delivered by C-section. Laboratory tests showed: Hemoglobin 83 g/L, hematocrit 0.24, WBC 6.97, platelets 270, creatinine 2.29 mg/dL, ↓ C3 0.20 g/L, ↑anti-dsDNA 1152.12 IU/mL, urine albumin 4+, RBC 90–95/hpf with dysmorphic RBCs, WBC 10–12/hpf, hyaline and granular casts. Anticardiolipin, lupus anticoagulant, anti-Ro and anti-La were negative.

Clinical course Prednisone was increased to 40 mg/day and she was started on methyldopa, azathioprine, HCQ, calcium plus vitamin D, iron plus folate, and aspirin 80 mg/d. A week later, she was admitted due to cough, dyspnea, orthopnea and low-grade fever. Chest radiograph showed hazy densities on both lung fields. Laboratory tests showed: Hemoglobin 74 g/L, hematocrit 0.22, WBC 17.20, platelets 433. Urine albumin 4+, RBC 18–22/hpf, WBC 10–15/hpf, hyaline, granular and waxy casts, urine total protein 822.40 mg/dL, urine creatinine 151.08 mg/dL, urine protein-creatinine ratio 5.44; BUN 62.6 mg/dL, creatinine 2.90 mg/dL, total protein 5.01 mg/dL, albumin 2.66 g/dL, Na 132 mmol/L, K 5.69 mmol/L, phosphorus 6.07 mmol/L, and iCa 1.19 mmol/L; SARS-CoV2 test was negative. She was started on antibiotics and received red cell transfusions; regular hemodialysis was initiated due to pulmonary congestion and metabolic acidosis.

Discussion Points

• Distinguish pre-eclampsia from LN flare

• Management of severe LN flare with renal insufficiency during pregnancy including the role of plasma exchange

Discussion Points Case 2: 22–year-old female with refractory LN despite immunosuppressive regimens and rituximab

Liz Lightstone, Sandra Navarra

Clinical data A 22-year-old female presented with anti-phospholipid syndrome (APS) and LN at age 8. She had completed cyclophosphamide induction therapy, had been adherent to MMF (plus tacrolimus for 18 months), and received eight doses of rituximab. Renal histopathology (2008, 2016, 2019) shows persistent lupus nephritis ISN/RPS Class IV, varying activity and chronicity indices. She would attain partial renal remission for a few months, but never achieved complete remission. Blood pressure and renal function remain within normal range.

Discussion Point

• Updates in the management of LN

Discussion Point Case 3: 35-year-old male with LN presents with persistent hypokalemia

Liz Lightstone, Sandra Navarra

Clinical data A 35-year-old male with LN ISN/RPS Class IV – S, activity 11 and chronicity 4, presented with nephrotic-range proteinuria, hypertension, and impaired renal function. Renal ultrasound was normal without calcinosis. He received prednisone, MMF, HCQ, anti-hypertensives, and calcium plus vitamin D. He had persistently low levels of serum potassium (K) 2.4–3.8 meqs/L, and serum bicarbonate (HCO3) 11–20 mmol/L despite K and HCO3 supplementation. Urine pH was 6.0, urine sodium (Na) 80 mmol/L, urine K 20.63 mmol/L, urine chloride (Cl) 97.90 mmol/L. Serum anion gap was normal, and urine anion gap positive at 2.73 meq/L, confirming the diagnosis of an underlying distal renal tubular acidosis (RTA).

Discussion Points

• Clinical significance and management of RTA in LN

Discussion Points Case 4: 31-year-old patient with LN and APS presents with fever, deteriorating kidney function and an ovarian mass

Liz Lightstone, Sandra Navarra

Clinical data A 31-year-old female was diagnosed with LN and APS 8 years ago presenting with Raynaud’s, mononeuritis multiplex, proteinuria, pancytopenia, and pericarditis. She was given methylprednisolone pulse, cyclophosphamide, and belimumab then maintained on hydroxychloroquine, MMF, aspirin, nifedipine, iron plus folate, and calcium plus vitamin D. She developed hematologic flare a year ago which responded well to methylprednisolone pulse and two doses of rituximab. Two months ago, she presented with intermittent fever, dysuria, and cough. Laboratory results were: Hemoglobin 97 g/L, WBC 8.4 x10⁹/L, platelet 10⁹ x10⁹/L, BUN 52.1 mmol/L, creatinine 2.73 mg/dL (eGFR 22.3 ml/min) →3.26 mg/dL (eGFR 18.1 ml/min), urine protein 2+, RBC 40–50, pus >100; urine PCR by Gene Xpert^® was positive for Mycobacterium tuberculosis (TB), no rifampicin resistance. Chest radiograph showed infiltrates suggestive of miliary TB. Abdominal ultrasound showed renal cysts with calcifications, mild left ureteropelvocaliectasia from a left adnexal cystic mass measuring 8.57 cm. Exploratory laparotomy with left salpingo-oophorectomy was performed; histopathology showed caseating granuloma. She was started on an anti-TB regimen.

Discussion Points

• Causes of renal insufficiency in a patient with LN

• Renal involvement in APS

Learning Objectives

• Describe management approach to LN

• Explain special considerations in the management of LN flare during pregnancy

• Discuss further management options in refractory LN

• Discuss clinical situations which significantly contribute to morbidity in LN