Light-chain proximal tubulopathy: a retrospective study from a single Chinese nephrology referral center

Figures & data

Figure 1. Study flow chart of patients with light-chain proximal tubulopathy (LCPT) who underwent kidney biopsies and pathological spectrum from jan. 2016 to nov. 2022.

Table 1. Demographic and clinical evaluation of patients with LCPT.

Characteristic	Patients(n = 19)
Demographic characteristics
Age, y	57 ± 11
Gender	6 F/13 M
Medical history
Hypertension, %	37
Diabetes, %	11
Disease courses
Median duration from onset to the biopsy, m	6 (range: 2-60)
Initial Symptoms
Proteinuria, %	74
Elevated serum creatinine (sCr), %	42
Fatigue, %	16
Nausea, %	11
Serum Studies
Baseline sCr, μmol/L	134.91 ± 79.15
Baseline eGFR, mL/min/1.73m2	59.640 ± 27.449
Albumin, g/L	42.1 ± 8.6
Hemoglobin, g/dl	124 ± 27
Urinary studies
Proteinuria (g/24 hr)	2.44 ± 1.89
N-acetyl-beta-glucosaminidase (NAG), U/L	34.8 ± 53.5
α1-microglobulin (A1M), mg/L	134.5 ± 127.8
Albumin-creatinine ratio (ACR), mg/gCr	205.67 ± 243.41
Hematuria	9
Renal characteristics
CKD stage (I, II, III, IV, V)	2, 5, 7, 1, 1
Fanconi Syndrome	2
AKI	1
Acute tubular injury (ATI)	14
Other disorders
Anemia	11
Hypokalemia	5
Hypophosphatemia	1
Hypocomplementemia	2

Table 2. Hematological evaluation and kidney biopsy findings of patients with LCPT.

LCPT Type*	I	II	III	IV
N	3	5	10	1
Light chain
κ (n = 16)	1	4	10	1
λ (n = 3)	2	1	/	/
Paraprotein	1 IgM λ	1 IgA λ	4 IgA κ	1 IgG κ
	1 λ only	2 IgG κ	1 IgA κ + κ
	1 κ only	1 negative	1 IgG κ
			1 κ only
			1 negative
Urine paraprotein	2 λ only	1 IgA λ + λ	5 κ only	1 IgG κ
	1 κ only	1 IgA κ	2 IgA κ
		2 negatives	1 IgG κ + κ
Hematologic diagnoses
MGRS (n = 10)	1	3	5	1
MM (n = 8)	1	2	5	/
NHL (n = 1)	1	/	/	/
Abnormal κ/λ ratio	2/2	3/5	6/6	1/1
Serum pathogenic FLC > 1000 mg/L	2/2	3/5	4/6	0/1

* LCPT was divided into four categories according to Herrera⁵ as described.

Figure 2. Pathologic features of LCPT by transmission electron microscopy (TEM). A) TEM showed the proximal tubular cells were occupied by crystals of varying size and shapes (×8000). B) the proximal tubular epithelial cells were variably distended by fibrillary cytoplasmic inclusions (×8000), with compression of the nuclear contours. C) The endosomes and lysosomes were increased and appeared round or ovoid which extended from the apical to the basal side of cytoplasm in a non-crystalline LCPT patient (×8000). D) PTCs of non-crystalline LCPT patients exhibited mitochondria swelling and fragmentation, which indicated the mitochondrial stress (×8000).

Table 3. Chemotherapeutic strategy and outcomes of LCPT patients.

LCPT Type	Hematologic diagnoses	Therapeutic agent	SCT	sCr (initial)	eGFR (initial)	sCr (final)	eGFR (final)	Hematologic outcomes	Follow-up time (m)
I	NHL	R-CHOP	No	48.59	98.767	43.9	101.406	SD	5
II	MGRS	Supportive	No	71.33	97.537	/	/	Un	38
	MM	BCD	Yes	68.6	101.119	83.6	88.985	sCR	17
III	MM	BCD	No	131.34	49.065	177	33.967	SD	53
	MM	BCD + BR	No	99.3	48.678	121.6	37.571	SD	22
	MGRS	BCD	No	137	46.953	/	/	Un	15
	MM	BCD + DVD	No	132.3	45.977	99.16	64.697	VGPR	15
	MM	BCD	Yes	193.7	33.607	134.3	51.961	CR	9

BCD: bortezomib + cyclophosphamide + dexamethasone; BR: lenalidomide + bortezomib; DVD: daratumumab + bortezomib + dexamethasone; R-CHOP, rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone.

CR, complete remission; sCR, stringent complete response; VGPR, very good partial response; SD, stable hematologic disease; Un: Unknown.