Age-related renal function decline in Fabry disease patients on enzyme replacement therapy: a longitudinal cohort study

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Nephropathy is common in Fabry disease (FD). Prior studies of renal function during enzyme replacement therapy (ERT) have primarily used estimated glomerular filtration rate (eGFR). We studied the attrition of renal function in FD by measured GFR (mGFR) and urine protein excretion, and explored the influence of age.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This was a long-term observational study of a nationwide, family-screened cohort of FD patients. All Danish genetically verified FD patients on ERT, without end-stage renal disease at baseline and with three or more mGFR values were included.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In all, 52 patients with consecutive mGFR values (n = 841) over median 7 years (range 1–13) were evaluated. Blood pressure remained normal and urine protein excretion was unchanged. Plasma globotriaosylceramide (Gb-3) levels normalized while plasma lyso-Gb-3 remained abnormal in 34% of patients. Baseline mGFR was 90 ± 3 mL/min/1.73 m2 and rate of renal function loss 0.9 ± 0.2 mL/min/1.73 m2/year. Baseline eGFR was 97 ± 5 mL/min/1.73 m2 and rate of renal function loss 0.8 ± 0.3 mL/min/1.73 m2/year. mGFR was age- adjusted to renal healthy non-FD subjects, giving a standard deviation score of −0.8 ± 0.2 with an annual slope of −0.03 ± 0.01 (P = 0.099), without differences between genders. Age grouping of age-adjusted data showed exaggerated renal function loss with age. Urine albumin–creatinine ratio (UACR) &amp;gt;300 mg/g was associated with faster renal function loss, independent of baseline mGFR, age and gender.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>ERT-treated FD patients did not have a faster attrition of renal function than renal healthy non-FD subjects (background population). The rate of renal function loss with age was independent of gender and predicted by high UACR. We suggest cautious interpretation of non-age-adjusted FD renal data.</jats:p> </jats:sec>

An expert consensus document on the management of cardiovascular manifestations of Fabry disease

“…Although NT‐proBNP concentrations may be raised in patients without echocardiographic evidence of LVH, the highest values are encountered in patients with LVH, diastolic dysfunction, reduced T1 relaxation times on CMRI mapping and myocardial fibrosis 183–185 . Elevated high sensitivity troponin indicates advanced disease and a worse prognosis 186 ( Table 2 ) 1,13,76,81,90,104,111,112,156,157,161,167,169,170,178,184,186–215 .…”

Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team

“…Graft and patient survival in Fabry patients are comparable with that of non-Fabry patients undergoing a kidney transplantation [ 47 , 48 , 49 , 50 ], although Fabry kidney transplant recipients have a higher mortality for cardiac events with functioning grafts as compared to non-Fabry controls [ 50 ]. Kidney transplantation is not able to replace the enzyme deficiency, since there is no cross-correction of the enzymatic defect between cells, and most transplanted patients may require enzyme replacement therapy for preventing the progression of the disease in other organs.…”

Renal Manifestations of Fabry Disease: A Narrative Review

“…59 Angiotensin II also contributes to nephropathy through vasoconstriction, as well as the spread of inflammation and fibrosis. 60 GL3 accumulation occurs in all types of kidney cells. The deposits increase with disease progression and, in addition to podocytes, they can be found in the epithelium of Bowman's capsule, in the mesangial and endothelial cells, in the smooth muscle cells of the arteries and arterioles, interstitial cells, and in the distal tubule.…”