3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?
Abstract Background and Aims Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with...
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| creator | Teran, Melissa Pilco Furlano, Monica Pybus, Marc Jiménez, Víctor Martínez Peris, Asunción Rius Gomez, Maria Vanessa Perez Redondo, Gerson Berna De Arizon, Leonor Fayos Ars, Elisabet Torra, Roser |
| description | Abstract
Background and Aims
Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with an increasing incidence with age and CKD grade. A possible association between pathogenic variants of collagen type IV and renal cysts has been described. This study investigates the presence of renal cysts in a large cohort of individuals with heterozygous pathogenic variants in COL4A3/COL4A4.
Method
We evaluated the presence of kidney cysts, kidney size and lithiasis by ultrasound in 162 individuals with pathogenic variants in COL4A3/COL4A4 without kidney replacement therapy. The correlation between kidney cysts and age, proteinuria, eGFR, causing gene and type of variant, was analysed. Genetic testing had been performed in index cases by next generation sequencing (NGS) of a kidney-disease gene panel containing more than 400 genes including COL4A3, COL4A4 and COL4A5 genes.
Results
153 patients with a heterozygous disease-causing variant in COL4A3 or COL4A4 and 9 patients with digenic/complex inheritance were included. The mean age at renal ultrasound was 46.19 years (SD 14.93) and the mean eGFR was 75 ml/min/1.73 m2 (SD 35 ml/min/1.73 m2). Renal cysts were present in 50% of patients (81/162) and were bilateral in 30.25%. The mean age of patients with renal cysts was 53.26 years vs. 39.12 years for those without, and the mean eGFR was 60ml/min/1.73 m2 vs. 89ml/min/1.73 m2 for patients with and without renal cysts. Only 2.5% (4/162) of patients had renal lithiasis. The mean kidney size was 104.05 mm (SD 13.86 mm) for the right kidney and 104.98 mm (SD 13.94 mm) for the left kidney. Cystic nephromegaly was observed in 3.7% (6/162). No correlation was found between renal cysts and gender (p = 0.632). Age and CKD stage had a positive correlation with the development of renal cysts (p = |
| doi_str_mv | 10.1093/ndt/gfad063c_3812 |
| format | Article |
| fullrecord | <record><control><sourceid>oup_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1093_ndt_gfad063c_3812</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/ndt/gfad063c_3812</oup_id><sourcerecordid>10.1093/ndt/gfad063c_3812</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1222-833c1e0fbd112f0539b54c0bfb7a7a45023bab0a2ff52014695beba76e1680763</originalsourceid><addsrcrecordid>eNqNkMFOhDAURRujiTj6Ae76ASKvLaWwMgQ7AxEoGVAzK9ICNRp1JqAL_17GcePO1U1uzn3JOwhdErgmEDHvvf_wnqzuIWBdy0JCj5BD_ABcykJ-jJyZIS5wiE7R2TS9AEBEhXBQvWdxvJb4Lrst5QYnm7qpcaHmJlFFoUqclbiSqsolfsyadG5zP2beT_i4iptUrWSZJfghXmdx2dQ35-jE6tdpuPjNBbpfyiZJ3VytsiTO3Y5QSt2QsY4MYE1PCLXAWWS434GxRmihfQ6UGW1AU2s5hfmZiJvBaBEMJAhBBGyByOFuN26naRxsuxuf3_T41RJo91ba2Ur7x8q8uTpstp-7f-DfB7Vdfw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Teran, Melissa Pilco ; Furlano, Monica ; Pybus, Marc ; Jiménez, Víctor Martínez ; Peris, Asunción Rius ; Gomez, Maria Vanessa Perez ; Redondo, Gerson Berna ; De Arizon, Leonor Fayos ; Ars, Elisabet ; Torra, Roser</creator><creatorcontrib>Teran, Melissa Pilco ; Furlano, Monica ; Pybus, Marc ; Jiménez, Víctor Martínez ; Peris, Asunción Rius ; Gomez, Maria Vanessa Perez ; Redondo, Gerson Berna ; De Arizon, Leonor Fayos ; Ars, Elisabet ; Torra, Roser</creatorcontrib><description>Abstract
Background and Aims
Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with an increasing incidence with age and CKD grade. A possible association between pathogenic variants of collagen type IV and renal cysts has been described. This study investigates the presence of renal cysts in a large cohort of individuals with heterozygous pathogenic variants in COL4A3/COL4A4.
Method
We evaluated the presence of kidney cysts, kidney size and lithiasis by ultrasound in 162 individuals with pathogenic variants in COL4A3/COL4A4 without kidney replacement therapy. The correlation between kidney cysts and age, proteinuria, eGFR, causing gene and type of variant, was analysed. Genetic testing had been performed in index cases by next generation sequencing (NGS) of a kidney-disease gene panel containing more than 400 genes including COL4A3, COL4A4 and COL4A5 genes.
Results
153 patients with a heterozygous disease-causing variant in COL4A3 or COL4A4 and 9 patients with digenic/complex inheritance were included. The mean age at renal ultrasound was 46.19 years (SD 14.93) and the mean eGFR was 75 ml/min/1.73 m2 (SD 35 ml/min/1.73 m2). Renal cysts were present in 50% of patients (81/162) and were bilateral in 30.25%. The mean age of patients with renal cysts was 53.26 years vs. 39.12 years for those without, and the mean eGFR was 60ml/min/1.73 m2 vs. 89ml/min/1.73 m2 for patients with and without renal cysts. Only 2.5% (4/162) of patients had renal lithiasis. The mean kidney size was 104.05 mm (SD 13.86 mm) for the right kidney and 104.98 mm (SD 13.94 mm) for the left kidney. Cystic nephromegaly was observed in 3.7% (6/162). No correlation was found between renal cysts and gender (p = 0.632). Age and CKD stage had a positive correlation with the development of renal cysts (p = <0.001) (Tables 1 and 2). Proteinuria was more common in individuals with renal cysts 61% vs 39% (p = 0.012), but was related to age and CKD stage. The presence of a kidney cyst did not correlate with the mutated gene or the type of variant.
Table 1:
Individuals with kidney cysts according to the age groups.
Age
<30
30-39
40-49
50-59
60-69
>70
Total
Patients (n)
21
32
38
41
25
5
162
Kidney cysts (KC)
3 (14,3%)
9 (28,1%)
18 (47,4%)
25 (61%)
21 (84%)
5 (100%)
81 (50%)
Unilateral KC
2 (9,5%)
2 (6,3%)
10 (26,3%)
5 (12,2%)
10 (40%)
3 (60%)
32 (19,8%)
Bilateral KC
1 (4,8%)
7 (21,9%)
8 (21,1%)
17 (41,5%)
14 (56%)
2 (40%)
49 (30,2%)
Table 2:
Individuals with kidney cysts according to chronic kidney disease (CKD) stage.
CKD Stage
1
2
3a
3b
4
5
Total
Patients (n)
63
38
17
26
12
6
162
Kidney cysts (KC)
20 (31,7%)
15 (39,5%)
13 (76,5%)
20 (76,9%)
8 (66,7%)
5 (83,3%)
81 (50%)
Unilateral KC
9 (14,3%)
9 (23,7%)
5 (29,4%)
6 (23,1%)
1 (8,3%)
2 (33,3%)
32 (19,8%)
Bilateral KC
11 (17,5%)
6 (15,8%)
8 (47,1%)
14 (53,8%)
7 (58,3%)
3 (50%)
49 (30,2%)
Conclusion
Individuals with COL4A3/COL4A4 pathogenic variants develop kidney cysts at a higher rate than age-matched healthy individuals, and their presence is also related to ageing, as in the general population. Gender is not relevant for the development of renal cysts, in contrast to the general population cohorts. Proteinuria and CKD grade correlate with the development of renal cysts but nephromegaly is rare. Renal cysts in heterozygous carriers of COL43 or COL4A4 pathogenic variants are common but have no clinical consequences.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfad063c_3812</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>Nephrology, dialysis, transplantation, 2023-06, Vol.38 (Supplement_1)</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the ERA. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Teran, Melissa Pilco</creatorcontrib><creatorcontrib>Furlano, Monica</creatorcontrib><creatorcontrib>Pybus, Marc</creatorcontrib><creatorcontrib>Jiménez, Víctor Martínez</creatorcontrib><creatorcontrib>Peris, Asunción Rius</creatorcontrib><creatorcontrib>Gomez, Maria Vanessa Perez</creatorcontrib><creatorcontrib>Redondo, Gerson Berna</creatorcontrib><creatorcontrib>De Arizon, Leonor Fayos</creatorcontrib><creatorcontrib>Ars, Elisabet</creatorcontrib><creatorcontrib>Torra, Roser</creatorcontrib><title>3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?</title><title>Nephrology, dialysis, transplantation</title><description>Abstract
Background and Aims
Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with an increasing incidence with age and CKD grade. A possible association between pathogenic variants of collagen type IV and renal cysts has been described. This study investigates the presence of renal cysts in a large cohort of individuals with heterozygous pathogenic variants in COL4A3/COL4A4.
Method
We evaluated the presence of kidney cysts, kidney size and lithiasis by ultrasound in 162 individuals with pathogenic variants in COL4A3/COL4A4 without kidney replacement therapy. The correlation between kidney cysts and age, proteinuria, eGFR, causing gene and type of variant, was analysed. Genetic testing had been performed in index cases by next generation sequencing (NGS) of a kidney-disease gene panel containing more than 400 genes including COL4A3, COL4A4 and COL4A5 genes.
Results
153 patients with a heterozygous disease-causing variant in COL4A3 or COL4A4 and 9 patients with digenic/complex inheritance were included. The mean age at renal ultrasound was 46.19 years (SD 14.93) and the mean eGFR was 75 ml/min/1.73 m2 (SD 35 ml/min/1.73 m2). Renal cysts were present in 50% of patients (81/162) and were bilateral in 30.25%. The mean age of patients with renal cysts was 53.26 years vs. 39.12 years for those without, and the mean eGFR was 60ml/min/1.73 m2 vs. 89ml/min/1.73 m2 for patients with and without renal cysts. Only 2.5% (4/162) of patients had renal lithiasis. The mean kidney size was 104.05 mm (SD 13.86 mm) for the right kidney and 104.98 mm (SD 13.94 mm) for the left kidney. Cystic nephromegaly was observed in 3.7% (6/162). No correlation was found between renal cysts and gender (p = 0.632). Age and CKD stage had a positive correlation with the development of renal cysts (p = <0.001) (Tables 1 and 2). Proteinuria was more common in individuals with renal cysts 61% vs 39% (p = 0.012), but was related to age and CKD stage. The presence of a kidney cyst did not correlate with the mutated gene or the type of variant.
Table 1:
Individuals with kidney cysts according to the age groups.
Age
<30
30-39
40-49
50-59
60-69
>70
Total
Patients (n)
21
32
38
41
25
5
162
Kidney cysts (KC)
3 (14,3%)
9 (28,1%)
18 (47,4%)
25 (61%)
21 (84%)
5 (100%)
81 (50%)
Unilateral KC
2 (9,5%)
2 (6,3%)
10 (26,3%)
5 (12,2%)
10 (40%)
3 (60%)
32 (19,8%)
Bilateral KC
1 (4,8%)
7 (21,9%)
8 (21,1%)
17 (41,5%)
14 (56%)
2 (40%)
49 (30,2%)
Table 2:
Individuals with kidney cysts according to chronic kidney disease (CKD) stage.
CKD Stage
1
2
3a
3b
4
5
Total
Patients (n)
63
38
17
26
12
6
162
Kidney cysts (KC)
20 (31,7%)
15 (39,5%)
13 (76,5%)
20 (76,9%)
8 (66,7%)
5 (83,3%)
81 (50%)
Unilateral KC
9 (14,3%)
9 (23,7%)
5 (29,4%)
6 (23,1%)
1 (8,3%)
2 (33,3%)
32 (19,8%)
Bilateral KC
11 (17,5%)
6 (15,8%)
8 (47,1%)
14 (53,8%)
7 (58,3%)
3 (50%)
49 (30,2%)
Conclusion
Individuals with COL4A3/COL4A4 pathogenic variants develop kidney cysts at a higher rate than age-matched healthy individuals, and their presence is also related to ageing, as in the general population. Gender is not relevant for the development of renal cysts, in contrast to the general population cohorts. Proteinuria and CKD grade correlate with the development of renal cysts but nephromegaly is rare. Renal cysts in heterozygous carriers of COL43 or COL4A4 pathogenic variants are common but have no clinical consequences.</description><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqNkMFOhDAURRujiTj6Ae76ASKvLaWwMgQ7AxEoGVAzK9ICNRp1JqAL_17GcePO1U1uzn3JOwhdErgmEDHvvf_wnqzuIWBdy0JCj5BD_ABcykJ-jJyZIS5wiE7R2TS9AEBEhXBQvWdxvJb4Lrst5QYnm7qpcaHmJlFFoUqclbiSqsolfsyadG5zP2beT_i4iptUrWSZJfghXmdx2dQ35-jE6tdpuPjNBbpfyiZJ3VytsiTO3Y5QSt2QsY4MYE1PCLXAWWS434GxRmihfQ6UGW1AU2s5hfmZiJvBaBEMJAhBBGyByOFuN26naRxsuxuf3_T41RJo91ba2Ur7x8q8uTpstp-7f-DfB7Vdfw</recordid><startdate>20230614</startdate><enddate>20230614</enddate><creator>Teran, Melissa Pilco</creator><creator>Furlano, Monica</creator><creator>Pybus, Marc</creator><creator>Jiménez, Víctor Martínez</creator><creator>Peris, Asunción Rius</creator><creator>Gomez, Maria Vanessa Perez</creator><creator>Redondo, Gerson Berna</creator><creator>De Arizon, Leonor Fayos</creator><creator>Ars, Elisabet</creator><creator>Torra, Roser</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20230614</creationdate><title>3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?</title><author>Teran, Melissa Pilco ; Furlano, Monica ; Pybus, Marc ; Jiménez, Víctor Martínez ; Peris, Asunción Rius ; Gomez, Maria Vanessa Perez ; Redondo, Gerson Berna ; De Arizon, Leonor Fayos ; Ars, Elisabet ; Torra, Roser</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1222-833c1e0fbd112f0539b54c0bfb7a7a45023bab0a2ff52014695beba76e1680763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teran, Melissa Pilco</creatorcontrib><creatorcontrib>Furlano, Monica</creatorcontrib><creatorcontrib>Pybus, Marc</creatorcontrib><creatorcontrib>Jiménez, Víctor Martínez</creatorcontrib><creatorcontrib>Peris, Asunción Rius</creatorcontrib><creatorcontrib>Gomez, Maria Vanessa Perez</creatorcontrib><creatorcontrib>Redondo, Gerson Berna</creatorcontrib><creatorcontrib>De Arizon, Leonor Fayos</creatorcontrib><creatorcontrib>Ars, Elisabet</creatorcontrib><creatorcontrib>Torra, Roser</creatorcontrib><collection>CrossRef</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teran, Melissa Pilco</au><au>Furlano, Monica</au><au>Pybus, Marc</au><au>Jiménez, Víctor Martínez</au><au>Peris, Asunción Rius</au><au>Gomez, Maria Vanessa Perez</au><au>Redondo, Gerson Berna</au><au>De Arizon, Leonor Fayos</au><au>Ars, Elisabet</au><au>Torra, Roser</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><date>2023-06-14</date><risdate>2023</risdate><volume>38</volume><issue>Supplement_1</issue><issn>0931-0509</issn><eissn>1460-2385</eissn><abstract>Abstract
Background and Aims
Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with an increasing incidence with age and CKD grade. A possible association between pathogenic variants of collagen type IV and renal cysts has been described. This study investigates the presence of renal cysts in a large cohort of individuals with heterozygous pathogenic variants in COL4A3/COL4A4.
Method
We evaluated the presence of kidney cysts, kidney size and lithiasis by ultrasound in 162 individuals with pathogenic variants in COL4A3/COL4A4 without kidney replacement therapy. The correlation between kidney cysts and age, proteinuria, eGFR, causing gene and type of variant, was analysed. Genetic testing had been performed in index cases by next generation sequencing (NGS) of a kidney-disease gene panel containing more than 400 genes including COL4A3, COL4A4 and COL4A5 genes.
Results
153 patients with a heterozygous disease-causing variant in COL4A3 or COL4A4 and 9 patients with digenic/complex inheritance were included. The mean age at renal ultrasound was 46.19 years (SD 14.93) and the mean eGFR was 75 ml/min/1.73 m2 (SD 35 ml/min/1.73 m2). Renal cysts were present in 50% of patients (81/162) and were bilateral in 30.25%. The mean age of patients with renal cysts was 53.26 years vs. 39.12 years for those without, and the mean eGFR was 60ml/min/1.73 m2 vs. 89ml/min/1.73 m2 for patients with and without renal cysts. Only 2.5% (4/162) of patients had renal lithiasis. The mean kidney size was 104.05 mm (SD 13.86 mm) for the right kidney and 104.98 mm (SD 13.94 mm) for the left kidney. Cystic nephromegaly was observed in 3.7% (6/162). No correlation was found between renal cysts and gender (p = 0.632). Age and CKD stage had a positive correlation with the development of renal cysts (p = <0.001) (Tables 1 and 2). Proteinuria was more common in individuals with renal cysts 61% vs 39% (p = 0.012), but was related to age and CKD stage. The presence of a kidney cyst did not correlate with the mutated gene or the type of variant.
Table 1:
Individuals with kidney cysts according to the age groups.
Age
<30
30-39
40-49
50-59
60-69
>70
Total
Patients (n)
21
32
38
41
25
5
162
Kidney cysts (KC)
3 (14,3%)
9 (28,1%)
18 (47,4%)
25 (61%)
21 (84%)
5 (100%)
81 (50%)
Unilateral KC
2 (9,5%)
2 (6,3%)
10 (26,3%)
5 (12,2%)
10 (40%)
3 (60%)
32 (19,8%)
Bilateral KC
1 (4,8%)
7 (21,9%)
8 (21,1%)
17 (41,5%)
14 (56%)
2 (40%)
49 (30,2%)
Table 2:
Individuals with kidney cysts according to chronic kidney disease (CKD) stage.
CKD Stage
1
2
3a
3b
4
5
Total
Patients (n)
63
38
17
26
12
6
162
Kidney cysts (KC)
20 (31,7%)
15 (39,5%)
13 (76,5%)
20 (76,9%)
8 (66,7%)
5 (83,3%)
81 (50%)
Unilateral KC
9 (14,3%)
9 (23,7%)
5 (29,4%)
6 (23,1%)
1 (8,3%)
2 (33,3%)
32 (19,8%)
Bilateral KC
11 (17,5%)
6 (15,8%)
8 (47,1%)
14 (53,8%)
7 (58,3%)
3 (50%)
49 (30,2%)
Conclusion
Individuals with COL4A3/COL4A4 pathogenic variants develop kidney cysts at a higher rate than age-matched healthy individuals, and their presence is also related to ageing, as in the general population. Gender is not relevant for the development of renal cysts, in contrast to the general population cohorts. Proteinuria and CKD grade correlate with the development of renal cysts but nephromegaly is rare. Renal cysts in heterozygous carriers of COL43 or COL4A4 pathogenic variants are common but have no clinical consequences.</abstract><pub>Oxford University Press</pub><doi>10.1093/ndt/gfad063c_3812</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_crossref_primary_10_1093_ndt_gfad063c_3812 |
| source | Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| title | 3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS? |
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