The first case of lipoprotein glomerulopathy complicated with collagen type III glomerulopathy and literature review

We report the first case of LPG and CG in the world. The patient was diagnosed with LPG and CG through laboratory examination, renal biopsy and WES results.

The patient presented with renal failure, elevated serum Apo E levels and the characteristic pathological manifestations of LPG. The glomerular capillaries were found to be distended by the lipoprotein thrombi under LM and EM. Immunofluorescence showed staining for APOA and APOB in the glomerular capillaries. Genetic testing further identified a pathogenic variant (c.127C>T; p. Arg43Cys) in exon 3 of the APOE gene inherited from his grandmother and mother without any clinical manifestations, which may be related to incomplete penetrance [7]. It has been defined as APOE -Kyoto of LPG [7].

To date, there is no specific treatment available for LPG. Glucocorticoids and immune suppressants were ineffective. DFPP and IA treatments were performed when the kidney function deteriorated. Immunoadsorption therapy seems more appropriate for this patient compared with DFPP. A search of the literature showed that IA and DFPP are the most common treatments for LPG, but which method is best is still controversial. Long-term follow up shows that IA can delay the progression of LPG. However, the decrease of immunoglobulin often leads to increase of infectious events. Therefore, since 2010, the National Clinical Research Center for Kidney Disease has suggested using DFPP to remove Apo E for the treatment of LPG, and DFPP has been identified as an effective method.

Renal pathology is the gold standard for the diagnosis of CG. LM and EM revealed that collagen III was deposited segmentally in the GBM and mesangial area. In addition, the serum PIIINP level, which is a noninvasive index for CG, was significantly increased [8]. CG may have a genetic basis, especially when presenting in childhood, but it is considered a sporadic disorder when it appears in adults [2]. No clear pathogenic gene was found. CG mainly occurs in elderly individuals, possibly because the accumulation of collagen occurs over a long time. Our case was diagnosed at the age of 21, which may be the result of interactions with the other kidney diseases.

There is no doubt about the diagnosis of LPG with CG in this patient. Although WES revealed three mutations in the COL4A gene, including two mutations in COL4A4 on chromosome 2 inherited from his father, one of which was reported as a suspected pathogenic mutation and the other was a VUS. Another VUS was found in COL4A5 on chromosome X inherited from his grandmother and mother. This genetic pattern does not conform to compound heterozygous inheritance or digenic disease that can cause Alport syndrome (ATS). In addition, the clinical and pathological manifestations of this patient do not support ATS, thus the diagnosis of ATS is not considered.

In conclusion, no confirmed cases of these two nephropathies occurring simultaneously have been reported in the literature. These rare diseases are related to metabolic abnormalities, and may highlight a close relationship between lipid metabolism and collagen synthesis.

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