A 26-year-old woman with massive proteinuria was diagnosed with this rheumatism due to dry skin?

For medical professionals only, please pay attention to every abnormal signal the body sends.
In the summer of 2017, a 26-year-old woman came to the hospital
.

The self-reported 1 week ago without obvious incentive to have a large amount of foam in the urine
.

When the doctor asked if there were any accompanying symptoms, she hesitated for a moment: "I feel that the skin is relatively dry, especially in the vagina.
.
.
It seems to have been uncomfortable for the past six months
.

" The doctor asked carefully, and the woman denied having oliguria, Gross hematuria, and no symptoms such as dry mouth, dry eyes, repeated parotid gland enlargement, flaky tooth loss, rash, arthralgia, and light allergy
.

 Outpatient laboratory urine routine: urine occult blood (+++), urine protein (+++), serum creatinine (Scr) 85.
6µmol/L
.

The doctor immediately admitted her to the hospital
.

 After she was admitted to the hospital, the doctor conducted a complete medical history inquiry and physical examination, and now provides the following meaningful results
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Past history: high blood pressure was found in 2012, the highest blood pressure was 180/110mmHg, oral labetalol and benidipine were administered, and blood pressure was generally controlled
.

 Physical examination: body temperature 36.
5°C, pulse 74 beats/min, respiration 19 breaths/min, blood pressure 180/100 mmHg, no superficial lymph nodes in the body, no positive signs in the heart, lungs, and abdomen, and no percussion pain in both kidneys.
There was no edema in the lower extremities
.

   Laboratory tests: blood routine: white blood cell count 5.
8×109/L, red blood cell count 4×1012/L, hemoglobin 118 g/L, platelet count 223×109/L; erythrocyte sedimentation rate 36mm/h; C-reactive protein 0.
92 mg/L L; Urine routine: urine occult blood (+++), urine protein (+++), microscopic red blood cells 5~10/high power field, urine protein amount 5.
02g/24h; blood biochemistry: alanine aminotransferase 13.
4 U/L, aspartate aminotransferase 15.
6U/L, albumin 34.
4g/L, globulin 25.
6g/L, urea nitrogen 5.
1mmol/L, Scr 85.
6µmol/L
.

 Urine protein components: urinary α1 microglobulin 112.
1 mg/L, urinary β2 microglobulin 80.
30 mg/L, urinary N-acetyl-β glucosaminidase 32.
6 U/L
.

 Immunological indicators: IgA 2.
38g/L, IgM 2.
28g/L, IgG 7.
17g/L, IgG4 0.
05g/L, complement C3 0.
13g/L, complement C4 0.
30g/L; rheumatoid factor 21.
53IU/ml; Anti-SSA antibody/Ro antibody (+)
.

The diagnosis revealed that the doctor suspected that the woman had primary Sjögren's syndrome (pSS), so the examination in this area was especially perfected, and the meaningful results are as follows
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 Dry eye 3 items: tear secretion test right 8mm, left 9mm, tear film break-up time right 7s, left 8s, corneal fluorescence staining (-)
.

 Saliva flow rate: saliva flow rate (basal) 0.
09ml/min, saliva flow rate (post-stimulation) 0.
5ml/min
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 The biopsy of labial gland showed mild reduction of acini, interstitial fat deposition, and lymphocyte count > 50/4 mm2
.

 Percutaneous renal biopsy was performed under the guidance of B-ultrasound, and the results are as follows: Figure 1.
Pathological changes of the patient's renal tissue
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A: lobulated hyperplasia of glomerular nodules, mild thickening of basement membrane, diffuse moderate to severe hyperplasia of mesangial cells and endothelial cells (HE×400); B: subepithelial, mesangial and subendothelial hyperplasia Hemoglobin deposition, with infiltration of individual neutrophils (Masson×400); C: slight thickening of the glomerular basement membrane, mesangial lysis, and segmental mesangial insertion (PASM×400); D: C3 ( 2+ to 3+) along the capillary wall and mesangial region in petal-like and clump-like deposits (immunofluorescence × 400)
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 Pathological diagnosis: membranous proliferative glomerulopathy with endothelial cell proliferation and neutrophil infiltration
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 The final clinical diagnosis: pSS combined with renal damage - membranous proliferative glomerulonephritis (MPGN)
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The treatment of pSS is mainly based on the invasion of exocrine glands such as lacrimal and salivary glands, and autoimmune diseases such as lung, stomach, kidney and other internal organs can also occur
.

In recent years, there have been more reports of pSS renal damage at home and abroad, but the pathological type manifested as MPGN is rare
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Reviewing domestic literature, only one case of pSS combined with MPGN was reported in 1984, and no relevant reports have been reported since
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 Faced with insufficient and successful reference treatment experience, the doctor frowned and began to extensively consult relevant domestic and foreign treatment guidelines
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 The treatment options for pSS renal damage in the "2019 European League Against Rheumatism Recommendations for Local and Systemic Treatment of Sjögren's Syndrome" are: glucocorticoids (GCs) as first-line therapy; for patients with intolerance or refractory GCs, immune Inhibitors are second-line therapy; biologics are third-line therapy
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Based on this recommendation, doctors treated the patient and followed up long-term
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 Figure 2.
Doubts and Difficulties in the Treatment and Outcome of Patients in the Diagnosis and Treatment Process ■ 1.
What is the basis for the diagnosis of pSS? According to the latest classification criteria of pSS of American College of Rheumatology/European League Against Rheumatism in 2016: labial gland pathology showed lymphocyte foci ≥1/4mm2 (3 points), anti-SSA antibody/Ro antibody positive (3 points), natural saliva Flow rate ≤ 0.
1ml/min (1 point), the total score of this patient is 7 points, inquire medical history and complete relevant examinations, excluding the history of head, neck and face radiotherapy, hepatitis C virus infection, AIDS, lymphoma, sarcoidosis, transplantation The diagnosis of pSS was established in cases of substance-versus-host disease, the use of anti-acetylcholine drugs (such as atropine, hyoscyamine, bromine, belladonna, etc.
) and IgG4-related diseases
.

  ■ 2.
Is MPGN primary or secondary? What is the pathological mechanism of pSS-induced MPGN? MPGN can be divided into primary and secondary according to the etiology
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Common secondary causes include hepatitis C infection, systemic lupus erythematosus, rheumatoid arthritis, and cryoglobulinemia, etc.
The above diseases can be excluded by perfecting relevant examinations
.

 The incidence of renal damage in pSS is 30% to 50%, mainly tubulointerstitial nephritis, which can be manifested as distal renal tubular acidosis, proximal renal tubular acidosis and Fanconi syndrome
.

 This patient's MPGN secondary to pSS is a rare case, mainly mediated by immune complexes or complement.
A large number of antibodies are produced, and the two form an immune complex that binds to the endothelial cells of the glomerular capillary loop to induce an inflammatory response
.

 ■ 3.
How to monitor the possible nephrotoxicity caused by cyclosporine in patients who have been added with cyclosporine? ①In the current clinical application of cyclosporine, it is an effective way to reduce the nephrotoxicity by controlling the blood drug concentration within a safe range and avoiding prolonged use; ②Regular monitoring of renal function and urinary microalbumin is the key to discovering cyclosporine-induced renal damage The main method of kidney biopsy is still the gold standard; (3) neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) are the most studied nephrotoxicity markers.
The concentration of NGAL in blood may be affected by a variety of factors and is not specific for renal injury, while urinary NGAL may be more reliable for monitoring cyclosporine-induced renal injury; the up-regulation of Kim-1 expression may be used as an early indicator with higher specificity.
Good; serum indoxyl sulfate may have more advantages for monitoring chronic cyclosporine-induced renal injury[2]
.

References: [1] Yin Juanjuan, Yu Zhuanzhuan, Liu Muqing, et al.
A case of Sjögren's syndrome complicated with membranous proliferative glomerulonephritis.
Chinese Journal of Nephrology, 2022, 38(03): 235-237.
DOI: 10.
3760/cma.
j.
cn441217-20210507-00035[2]Chen Yongqi, Wu Ying.
Research progress of cyclosporine A-related nephrotoxicity markers[J].
International Journal of Pediatrics,2015,42 (3): 287- 290.
DOI: 10.
3760/cma.
j.
issn.
1673-4408.
2015.
03.
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