At the age of 35, her hair loss, edema, and anuria were caused by this tiny cell!

*It is only for medical professionals to read and refer to a rare and difficult case, let's learn it together! In line with the original intention of "spreading the strongest rheumatism and creating a new academic fashion", on the occasion of leaving the old and welcoming the new, the "medical world" media teamed up with nearly 20 well-known experts in the field of rheumatism from the four top rheumatology departments in China, covering 8 rheumatism In the field of hot diseases, we will start the "Rheumatism and the Waves-2020 Annual Rheumatism Inventory".

In this issue, Dr.
Song Zhibo from Peking University First Hospital shared with us a case analysis related to systemic lupus erythematosus (SLE).

1 The young woman was diagnosed with SLE and lupus nephritis (LN).
The patient is a 35-year-old woman with hair loss for more than 6 months, a rash for 2 weeks (facial rash, oral anti-allergic drugs and topical drugs are invalid), edema, anuria1 week.

The patient had been examined in the laboratory of an outside hospital, and the results were as follows: •Urine routine: urine protein (pro) 4+, urine occult blood (BLD) +/-; • biochemical: albumin (Alb) 17.
4g/L, creatinine (Scr) 258.
8μmol/L; • Complement: C3 0.
23g/L, C4＜0.
073g/L; • Anti-nuclear antibody (ANA) (+), anti-dsDNA antibody (+), anti-Sm antibody, anti-Sjogren’s syndrome antibody (SSA) ), anti-nRNP antibody is positive.

According to the examination results, the outside hospital considered it to be SLE.
He was treated with prednisone acetate 30 mg Qd and hydroxychloroquine for 3 days.
At the same time, diuretic treatment did not improve.

Therefore, he came to Peking University Hospital for treatment and was given prednisolone acetate 60mg Qd and furosemide 40mg Qd, but no improvement.

The patient had no oral ulcers, arthralgias, myalgias, Raynaud's phenomenon, etc.
during the course of the disease.
Since the onset, he has had poor diet, poor sleep, urinated as mentioned above, stools were normal, and his weight gained 5 kg.

When the patient was admitted to the hospital, his vital signs were stable, except for a slightly higher blood pressure (144/100mmHg).

The admission was diagnosed as SLE with LN and acute kidney injury (AKI).

The characteristics of this case are summarized as follows: • Young female, acute exacerbation of the chronic course; • Alopecia, butterfly erythema, edema, and anuria; • Nephrotic syndrome (NS) with AKI; • ANA (+), anti-dsDNA antibody, anti-Sm Antibodies, anti-nRNP antibodies, anti-SSA (+), and complement were significantly reduced.

After admission, the auxiliary examination showed lymphopenia, mild anemia, and obvious decrease in albumin: • Blood routine: white blood cell (WBC) 4×109/L, LY 0.
7×109/L, hemoglobin (Hb) 117g/L, platelet (PLT) ) 163×109/L; • Biochemical: Alb 20.
3g/L, Scr 576.
1μmol/L • C3 0.
25g/L, C4 0.
054g/L; • ANA 1:10000 (S) 1:100 (C), anti dsDNA antibody (IIF) 1:100/(ELISA) 385 IU/ml, anti-Sm antibody, anti-nRNP antibody, anti-SSA (+); • anti-phospholipid antibody (-); ANCA, anti-glomerular basement membrane (GBM) Antibody (-); • Direct Coombs' test (+); • Peripheral blood fragmentation of red blood cells by 0.
5%; • Kidney ultrasound: Both kidneys increase in volume, and both kidney parenchymal echoes are enhanced.

2 To confirm the diagnosis, the culprit turned out to be podocyte disease! For such a patient with a clear diagnosis of SLE, we need to solve her kidney problems as soon as possible.

First of all, it is necessary to judge whether she has a history of chronic kidney disease, or if she has only recently developed AKI.

Reviewing the medical history, the specific manifestations of this patient’s renal insufficiency are as follows: • Anuria for 1 week, with a progressive increase in serum creatinine; • Temporarily no obvious renal anemia, mineral and bone metabolism disorders, etc.
; • Renal B ultrasound: double kidney volume Enlarged, the echo of both kidney parenchyma increases.

What is the cause of her AKI? A follow-up of the medical history shows that the patient strictly limits the amount of urine after the urine output is reduced.
Insufficient prerenal volume may cause his AKI to aggravate, but this is not the most important factor.

From the results of abdominal and pelvic CT/B ultrasound without space-occupying lesions, postrenal factors can be excluded.

Therefore, it is believed that the patients' AKI is mainly caused by renal factors.

Kidney-related tests were performed for him, and the results were as follows: •Urine routine: pro4+, red blood cell (RBC) 10-20/HP, epithelial cell 10-20/HP; • Premature renal damage: urinary transferrin 691mg/L, N -Acetyl-β-D-glucosidase (NAG) 176.
7U/L, urine α1-MG 57.
2mg/L, urine immunoglobulin 1550mg/L; • 24-hour urine protein quantification (UTP): 3.
62g/100ml; •Urine protein electrophoresis: small molecule protein 40.
2%, albumin 51.
2%, macromolecular protein 8.
6%; •Formed element analysis: RBC 10~12/HPF slightly deformed, WBC 5~8/HPF, waxy, mixed tube Type occasionally; • Double kidney ultrasound: increased volume of both kidneys (RK 13.
6cm×6.
5cm×5.
9cm, parenchymal thickness 2.
1cm, LK 13.
3cm×6.
1cm×4.
8cm, parenchymal thickness 1.
6cm), both kidney parenchymal echo Enhanced; • Renal arteriovenous ultrasound (-).

Considering the renal factors of the patient may include the following reasons: • Proteinuria in nephropathy, with deformed red blood cells, suggesting glomerular damage; • Anuria, white blood cell urine, increased proportion of small molecular proteins in urine protein electrophoresis, and increased NAG enzyme , Suggesting that there is renal tubular injury, there may be acute tubular necrosis; • Eosinophils are not high, there is no clear drug, infection and other triggers, and the evidence of interstitial nephritis is insufficient; • Renal blood vessels, renal arteries and veins (-), Peripheral blood crushed 0.
5% of red blood cells, but platelets, reticulocytes, and LDH were not low, so there was no obvious abnormality.

Based on the results of these examinations, it is considered that the patient may be proliferative LN type IV, and may be associated with crescentic nephritis.

The patient's AKI supports this diagnosis, but the patient's urine formed elements are not prominent, and the urine output is significantly reduced.
This is not a typical manifestation of proliferative LN.

The patient was first treated with methylprednisolone 80mg Qd and subsequent methylprednisolone 120mg Qd.

Induction of dialysis for 3 days, after which maintenance hemodialysis 3 times a week.

After volume expansion and diuresis, the patient's urine output did not change significantly.

Next, a kidney biopsy was performed for the patient to confirm the clinical inference of proliferative LN type IV with crescentic nephritis.

If this inference can be confirmed, it is in line with the indications for hormone shock therapy.

However, after completing the renal puncture, it was found that the pathological characteristics did not meet the previous inference (Figure 1), there was no trace of proliferative LN, and no crescent formation.

The pathological results suggested that the patient had mild mesangial proliferative type II LN with acute tubular injury, and podocyte disease was considered.

What the electron microscope sees is consistent with the light microscope.

 Figure 1 Pathological results Type Ⅱ LN cannot explain the symptoms of the patient.
Can podocyte disease explain it? Figure 2 Schematic diagram of glomerulus and what is podocyte 3-podocyte disease and how to treat it? Podocytes, the epithelial cells of the visceral layer of the renal capsule, are attached to the outside of the glomerular basement membrane, and together with the basement membrane and glomerular endothelial cell layer constitute the glomerular blood filtration barrier.

Lupus podocyte disease is relatively rare clinically, and there is currently no recognized diagnostic criteria.

Columbia University believes that the diagnosis of lupus podocyte disease needs to meet the four conditions of clinical manifestations, light microscopy, immunofluorescence and electron microscopy.
The Nanjing Military Region General Hospital of my country also proposed similar standards (Table 1).

Table 1 Diagnostic criteria for lupus podocyte disease Lupus podocyte disease accounts for 0.
6% to 1.
5% of LN.
The extrarenal manifestations have the highest incidence of blood system damage, followed by facial erythema and joint pain.

The main manifestations under light microscope are mesangial hyperplasia (MsP), mild lesions (MCD) and focal segmental glomerulosclerosis (FSGS).

The Nanjing Military Region General Hospital has reported 50 cases of lupus podocyte disease, including 28 cases of MsP, 13 cases of MCD, and 9 cases of FSGS.

AKI occurred in 34% of patients with lupus podocyte disease, and the incidence of AKI in patients with FSGS of glomerulopathy (77.
8%) was significantly higher than that in patients with MCD or MsP (24.
4%).
Patients with AKI often had severe acute tubular interstitial injury Or acute tubular necrosis.

In this case, the light microscope showed MsP.
What are the special clinical features of this type of patient? Studies have found that in patients with podocyte disease, the level of NAG enzyme is significantly increased, suggesting that there may be renal tubular damage, and the proportion of AKI is significantly increased. Through literature study, we found that the specific mechanism of AKI is still unknown, which may be related to tubulointerstitial damage and insufficient circulation capacity.

The proportion of renal tubular epithelial cell cytoplasm or tubular basement membrane immunoglobulin and/or complement deposition was significantly higher than that of patients without AKI, indicating that the immune damage mechanism may be involved in the tubular interstitial damage of lupus podocyte disease.

In terms of treatment, patients with MCD or MsP lupus podocytes are treated with hormones or hormones combined with immunosuppressants alone, and the complete remission rate can reach 90%; for FSGS lupus podocytes, the complete remission rate is 22.
2%.

However, the recurrence rate is relatively high, reaching 30.
8% to 42.
86%.

Back to this patient, she had type II lupus nephritis combined with podocyte disease, and the clinical manifestations were AKI, but there was no indication of hormone shock, and the treatment would be different from crescentic nephritis or proliferative nephritis.

Therefore, adjust the treatment plan according to the pathological results as follows: • Reduce the dose of methylprednisolone to 80 mg Qd and 60 mg Qd after 1 week; • Monitor intake and output and weight, intermittent dialysis, and intermittent plasma and albumin expansion; • Due to renal function Insufficiency, postpone the addition of immunosuppressive agents, ACEI drugs, etc.

About 1 month later, the patient's urine output began to recover, the number of dialysis and ultrafiltration was gradually reduced in treatment, and the lupus activity index was also significantly improved.

When discharged from the hospital, the patient was completely out of dialysis, and the edema and abdominal distension were improved; the 24-hour urine protein was still high, albumin was low, but creatinine was significantly reduced; the serum index was stable.

Discharge medications include prednisone acetate 60 mg Qd, tacrolimus 1 mg Bid, hydroxychloroquine sulfate tablets 100 mg Tid, fosinopril 20 mg Qd, nifedipine controlled release tablets 30 mg Bid, calcium carbonate 750 mg Tid, and calcitriol 0.
25 μg Qn.

The follow-up results 3 months after discharge showed that the general condition was good, there was no edema, the urine protein was completely negative, the creatinine and serological indicators were stable, and the complement and anti-dsDNA antibodies were normal.

In recent years, the clinical manifestations and treatment recommendations of lupus podocyte disease are rarely seen in the literature.

The U.
S.
Kidney Disease Guidelines updated in June 2020 mentioned LN and involved podocyte disease for the first time, and pointed out that after 90% of patients receive hormone monotherapy, the median time to remission is 4 weeks; hormone reduction is prone to relapse, which can be considered Maintenance therapy with low-dose hormones and immunosuppressive agents.

4 Summary • Kidney biopsy is very important for LN; • More thinking is needed when clinical and pathological discrepancies are needed; • Lupus with AKI is not all proliferative LN or with crescentic nephritis; • Type I or type II LN clinical manifestations are The level of proteinuria in kidney disease needs to be considered for lupus podocyte disease; • Lupus podocyte disease as a special pathological type needs attention.

Expert profile Dr.
Zhibo Song graduated from Peking University Medical School's eight-year program in clinical medicine in 2014, and received a doctorate degree in internal medicine, Peking University First Hospital.
Currently, he is the attending physician of the Department of Rheumatology and Immunology, Peking University First Hospital.
2016 and Participated in the "EULAR Certified Musculoskeletal Ultrasound Primary and Intermediate Training" in 2019 and obtained the "EULAR Certified Musculoskeletal Ultrasound Qualification Certificate".
Member of Peking University's Anti-epidemic Medical Team in 2020.
Outstanding Communist Party Member of Peking University