Systematic review and meta-analysis of the clinical features of MGRS.

BACKGROUND: It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney diseases. However, there have been few studies with large sample sizes, and their findings were inconsistent. This study aimed to conduct a meta-analysis of MGRS to describe the general characteristics of MGRS and its predictive factors. METHODS: Cohort or case-control studies published through December 2022 and related to clinicopathological features of MGRS were retrieved from the PubMed, Cochrane Library, Web of Science, Scopus, and Embase databases. Two researchers searched for studies that met the inclusion criteria. In the univariate analysis, fixed- or random- effects models were used to obtain pooled estimates of the weighted mean difference (WMD) and odds ratio (OR) for risk factors. In the multivariate analysis, the ORs of the independent risk factors from each study were pooled after transforming the original estimates. RESULTS: The meta-analysis included six studies. Univariate analysis showed that the following variables were statistically significant in MGRS: age (WMD = 1.78, 95%CI 0.21-3.35), hypertension (OR = 0.54, 95%CI 0.4-0.73), diabetes (OR = 0.42, 95%CI 0.29-0.59), albumin (WMD = - 0.26, 95%CI - 0.38--0.14), urinary protein level (WMD = 0.76, 95%CI 0.31-1.2), urinary protein ≥ 1.5 g/d (OR = 1.98, 95%CI 1.46-2.68), lambda-chain value (WMD = 29.02, 95%CI 16.55-41.49), abnormal free light-chain ratio (OR = 4.16, 95%CI 1.65-10.47), bone marrow puncture rate (OR = 5.11, 95% CI 1.31-19.95), and abnormal bone marrow outcome rate (OR = 9.63, 95%CI 1.98-46.88). Multivariate analysis showed urinary protein ≥ 1.5 g/d (OR = 2.80, 95%CI 1.53-5.15) and an abnormal free light-chain ratio (OR = 6.98, 95%CI 4.10-11.91) were associated with predictors of MGRS. CONCLUSIONS: Compared with non-MGRS patients with monoclonal gammopathy and concomitant kidney diseases, patients with MGRS were older, had fewer underlying diseases, more urinary protein, more abnormal free light-chain ratio, and more abnormal bone marrow results. Urinary protein ≥ 1.5 g/d and an abnormal free light-chain ratio were independent risk factors for MGRS.

Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis.

Introduction: Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. Methods: Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and in vitro functional study were conducted to verify variant pathogenicity. Results: Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the ε3/ε3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with α-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. Conclusion: LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions.