Clinicopathological features and outcomes of coexistent light chain cast nephropathy and light chain deposition disease in patients with newly diagnosed multiple myeloma.

AIMS: A varying proportion of patients with multiple myeloma suffer from more than one type of kidney disease simultaneously, of which the most common pattern is coexistent light chain cast nephropathy and light chain deposition disease (LCCN+LCDD). We investigated clinicopathological characteristics and outcomes of LCCN+LCDD in comparison with pure LCCN and pure LCDD. METHODS: We retrospectively analysed 45 newly diagnosed multiple myeloma patients with pure LCCN (n=26), LCCN +LCDD (n=9) and pure LCDD (n=10) between 2000 and 2019 at Peking University First Hospital. RESULTS: Pathologically, patients with LCCN+LCDD were more likely to have λ light chain isotype and presented atypical features of LCDD including less nodular glomerulosclerosis and less deposit distribution than patients with pure LCDD. In clinical characteristics, patients with LCCN +LCDD and patients with pure LCCN shared similar features. The death-censored renal survival in patients with LCCN +LCDD was similar to patients with pure LCCN but worse than patients with pure LCDD, but the overall survival was much better than patients with LCCN alone and similar to patients with pure LCDD. For patients with pure LCCN, the independent predictor of death-censored renal survival was lactate dehydrogenase, and the independent predictors of overall survival were the mean number of casts and serum albumin. CONCLUSIONS: Patients with LCCN+LCDD had similar renal outcome compared with patients with pure LCCN but the overall survival is much better. Thus, for patients with LCCN, especially those with λ restriction, pathologists should carefully evaluate the kidney specimens to exclude the possibility of combined LCDD.

Unveiling the Features of Mercury-Associated Minimal Change Disease: Comparison with Primary Minimal Change Disease.

INTRODUCTION: Long-term exposure to mercury can cause minimal change disease. However, the current understanding of mercury-associated minimal change disease (M-MCD) is inadequate. To improve the understanding of M-MCD, this study retrospectively analyzed the clinicopathological, ultrastructural, and prognostic features of M-MCD, in comparison with primary minimal change disease (P-MCD). METHODS: We retrospectively analyzed the clinicopathological data of 21 M-MCD patients and 21 P-MCD patients. Electron micrographs of glomerular capillaries were taken, and the foot process width (FPW) was measured. A receiver operating characteristics (ROC) curve analysis was performed to determine the optimum cutoff value of FPW that can differentiate the M-MCD from P-MCD. RESULTS: M-MCD patients presented similar clinical and routine pathological characteristics with P-MCD patients but had lower levels of FPW (935.0 [interquartile range (IQR) 853.7-1,176.7] nm vs. 1,403.2 [IQR 1,089.2-1,841.8] nm, p = 0.002). ROC curve analysis showed that FPW value below 1,385 nm might help to differentiate M-MCD from P-MCD (area under the curve of 0.787, sensitivity of 94.7%, and specificity of 52.4%). For patients with M-MCD, 77.8% achieved complete remission after mercury detoxification monotherapy. Patients with M-MCD had a lower relapse rate than patients with P-MCD (0 vs. 47.1%, p = 0.003). In addition, there was no significant difference in remission time between M-MCD patients treated with mercury detoxification monotherapy and those initially treated with immunosuppressive therapy (2.0 [IQR 1.0-6.0] months vs. 2.0 [IQR 1.5-2.5] months, p = 0.606). CONCLUSIONS: M-MCD patients showed similar clinicopathological features with P-MCD patients, but with less severe foot process effacement, suggesting different pathogenesis of these 2 disease entities. The treatment of mercury detoxification was highly effective for patients with M-MCD and can be considered as a primary choice in clinical practice.

Comparison of Ultrastructural Features Between Patients with Mercury-associated Membranous Nephropathy and Idiopathic Membranous Nephropathy.

BACKGROUND: Prolonged exposure to mercury can cause membranous nephropathy. Mercury-associated membranous nephropathy (M-MN) and idiopathic membranous nephropathy (I-MN) have similar clinical manifestations, making misdiagnoses likely. We compared the clinicopathological and ultrastructural features of M-MN and I-MN. METHODS: We retrospectively analyzed the clinicopathological data of 13 M-MN patients and 13 I-MN patients. Electron micrographs of glomerular capillaries were taken, and foot process width (FPW) and the number of foot processes per 10 µm glomerular basement membrane (GBM) were calculated. The presence and location of electron-dense deposits were recorded. RESULTS: Compared with I-MN patients, M-MN patients were younger (38.7 ±â€¯8.5 versus 45.8 ±â€¯5.7 years, P = 0.020), achieved complete remission more quickly (9.0 ±â€¯6.1 versus 20.3 ±â€¯9.8 months, P = 0.004), and had a lower relapse rate (0 versus 45.5%, P = 0.014). Patients with M-MN also had lower FPW (974.3 [interquartile range or IQR, 791.2-1504.4] nm versus 2370.6 [IQR, 2219.4-2559.1] nm, P = 0.001), more foot processes per 10 µm GBM (8.1 [IQR, 5.2-10.0] versus 3.3 [IQR, 3.1-3.5], P = 0.001), and a higher rate of mesangial electron-dense deposits (41.7% versus 0, P = 0.015). A cut-off FPW of <1654 nm differentiated M-MN from I-MN with high sensitivity (92.3%) and specificity (83.3%). CONCLUSIONS: Foot process effacement was less severe in M-MN than in I-MN. In patients with mercury toxic exposure, MN with less severe foot processes effacement suggested mercury could be the cause. Better prognosis in patients with M-MN may be associated with minor podocyte damage.

A non-invasive differential diagnostic model for light chain cast nephropathy in newly diagnosed multiple myeloma patients with renal involvement: a multicenter study.

OBJECTIVE: Light chain cast nephropathy is the most common form of renal lesion in multiple myeloma. Kidney impairment caused by light chain cast nephropathy can be reversed and survival can be improved if early diagnosis is available. It is thus of imperative importance to develop a non-invasive method to diagnose light chain cast nephropathy once the kidney biopsy is not always applicable. METHODS: We consecutively screened newly diagnosed multiple myeloma patients with kidney biopsies from 4 centers in China. Kidney pathologies were reviewed and clinical presentations were recorded. Then a diagnostic model was established by logistic regression and the predictive values were assessed. RESULTS: Between 1 June 1999 and 30 June 2019, a kidney biopsy was performed in 94 patients with newly diagnosed multiple myeloma, and light chain cast nephropathy was the most common pattern, seen in 52% of biopsied patients. The diagnostic model was established by multivariate logistic regression analysis as P(z) = 1/(1 + e-z) and z = - 0.093 Hemoglobin (g/L) + 0.421 Serum albumin (g/L) + 3.463 Acute kidney injury (0/1) - 9.207 High-density lipoprotein (mmol/L). If P(z) ≥ 0.55, the diagnosis pointed to light chain cast nephropathy; if P(z) < 0.55, the diagnosis favored non-light chain cast nephropathy. The area under the receiver operating characteristic curves was 0.981 (95% CI 0.959, 1.000). The model had a sensitivity of 93.9%, a specificity of 95.6%, a positive predictive value of 96.0%, a negative predictive value of 94.0%, and a total consistency of 95.0%. CONCLUSION: We built a novel, non-invasive diagnostic model through a multicenter study, which may be helpful in the diagnosis of light chain cast nephropathy in newly diagnosed multiple myeloma patients.

Decitabine-induced kidney thrombotic microangiopathy with glomerular crescents formation and tubular necrosis: A case report.

INTRODUCTION: Chemotherapeutic agents of direct cell damage play a role in initiating thrombotic microangiopathy (TMA), however still being underdiagnosed. Decitabine (DAC) is a pyrimidine analogue of the nucleoside cytidine, which can lead to injury to endothelium. Biopsy-proven DAC-induced kidney injury is rare. PATIENT CONCERNS: A 47-year-old Chinese man with membranous nephropathy presented recurrent edema and acute kidney injury after a 3-day course of low dose DAC infusion because of cyclophosphamide-relating thrombocytopenia. DIAGNOSIS: Laboratory data revealed nephrotic syndrome, hematuria, renal glycosuria and hypokalemia with hyperchloridemia. Renal pathological findings revealed TMA with secondary glomerular crescents formation (28%), partial foot process effacement and acute tubular necrosis. A diagnosis of DAC-induced renal TMA was considered. INTERVENTIONS: As DAC had been timely discontinued before admission, the patient only received supportive treatment. OUTCOMES: The patient achieved rapid remission of acute kidney injury after DAC withdrawal, and his serum creatinine further decreased to normal level after 6 months. CONCLUSION: Careful monitoring of renal function especially serum creatinine should be emphasized during DAC treatment.

Mercury-associated glomerulonephritis: a retrospective study of 35 cases in a single Chinese center.

BACKGROUND: Long-term exposure of mercury may induce glomerulonephritis. Clinical and pathological features of mercury-associated glomerulonephritis are not fully clear. This study retrospectively analyzed 35 cases of mercury-associated glomerulonephritis in a single Chinese center. METHODS: Thirty-five patients of mercury-associated glomerulonephritis were enrolled. Clinical data on diagnosis and during follow-up were collected. Plasma anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R and glomerular IgG subclasses deposition were detected in the cases with membranous nephropathy (MN). RESULTS: Mercury exposure was caused by skin lighting cream (20 patients), mercury-containing pills (9 patients), hair-dyeing agents (4 patients), and unidentified reasons (2 patients). All patients presented with proteinuria and normal renal function. The median of urinary protein was 4.6 (range 1.6~19.7) g/24 h. Twenty-two patients (62.9%) had nephrotic syndrome. Renal histopathology showed minimal change disease (MCD) in 21 patients (60.0%), MN in 13 (37.1%) and focal segmental glomerular sclerosis (FSGS) in 1 patient (2.9%). The proportion of MCD increased along with urinary mercury concentration (P = 0.024). In 13 cases of MN, all patients were negative for plasma anti-PLA2R antibody and glomerular PLA2R antigen. IgG1 (61.5%) and IgG4 (46.2%) deposits were noted along the glomerular capillary loops. Among the 16 patients received mercury detoxification monotherapy, 14 patients received 4.5 ± 2.8 (range 1~12) rounds of regimen and achieved complete remission in 4.5 (range 0.3~23.0) months, 2 patients stayed no remission. CONCLUSIONS: MCD was the most common pathological type of mercury-associated glomerulonephritis, followed by MN. The proportion of MCD increased along with the increase of urinary mercury concentration. Most patients could achieve complete remission after mercury detoxification.