PKD1 Truncating Mutations Accelerate eGFR Decline in Autosomal Dominant Polycystic Kidney Disease Patients.
Am J Nephrol
; 55(3): 380-388, 2024.
Article
en En
| MEDLINE
| ID: mdl-38194940
ABSTRACT
INTRODUCTION:
Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disease characterized by the accumulation of fluid-filled cysts in the kidneys, leading to renal volume enlargement and progressive kidney function impairment. Disease severity, though, may vary due to allelic and genetic heterogeneity. This study aimed to determine genotype-phenotype correlations between PKD1 truncating and non-truncating mutations and kidney function decline in ADPKD patients.METHODS:
We established a single-center retrospective cohort study in Kuwait where we followed every patient with a confirmed PKD1-ADPKD diagnosis clinically and genetically. Renal function tests were performed annually. We fitted generalized additive mixed effects models with random intercepts for each individual to analyze repeated measures of kidney function across mutation type. We then calculated survival time to kidney failure in a cox proportional hazards model. Models were adjusted for sex, age at visit, and birth year.RESULTS:
The study included 22 truncating and 20 non-truncating (42 total) patients followed for an average of 6.6 years (range 1-12 years). Those with PKD1 truncating mutations had a more rapid rate of eGFR decline (-4.7 mL/min/1.73 m2 per year; 95% CI -5.0, -4.4) compared to patients with PKD1 non-truncating mutations (-3.5 mL/min/1.73 m2 per year; 95% CI -4.0, -3.1) (p for interaction <0.001). Kaplan-Meier survival analysis of time to kidney failure showed that patients with PKD1 truncating mutations had a shorter renal survival time (median 51 years) compared to those with non-truncating mutations (median 56 years) (P for log-rank = 0.008).CONCLUSION:
In longitudinal and survival analyses, patients with PKD1 truncating mutations showed a faster decline in kidney function compared to patients PKD1 non-truncating mutations. Early identification of patients with PKD1 truncating mutations can, at best, inform early clinical interventions or, at least, help suggest aggressive monitoring.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Riñón Poliquístico Autosómico Dominante
/
Canales Catiónicos TRPP
/
Tasa de Filtración Glomerular
/
Mutación
Tipo de estudio:
Observational_studies
Límite:
Adult
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Female
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Humans
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Male
/
Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Am J Nephrol
/
Am. j. nephrol
/
American journal of nephrology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Kuwait